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The Indian Journal of Medical Research logoLink to The Indian Journal of Medical Research
. 2021 Jan-Feb;153(1-2):26–63. doi: 10.4103/ijmr.IJMR_2556_20

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India

M Vishnu Vardhana Rao , Atul Juneja , Mohua Maulik *,, Tulsi Adhikari , Saurabh Sharma , Jyotsna Gupta *, Yashmin Panchal *, Neha Yadav *
PMCID: PMC8184082  PMID: 33818466

Abstract

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

Keywords: Ayurveda, Yoga and Naturopathy, Unani, Siddha, Homeopathy; clinical trials; CTRI-India; convalescent plasma therapy; COVID-19; drug trials; registration; vaccine trials


The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported from Wuhan, China, in December 2019. Since then, the disease has spread worldwide and as of June 5, 2020, there were 6,824,499 cases and 408,307 deaths globally1.

In the absence of any vaccine or definitive therapeutic strategy, medical scientists are working tirelessly to not only save lives but also search for effective treatment modalities against the deadly virus. Drug development is a costly and time-consuming process and is not feasible in the context of the immediate global challenge. Therefore, drug repurposing strategies are being considered to develop safe and effective treatment regimens against the disease. Currently, an array of drugs used for the other health conditions are being studied for the treatment of COVID-19 in several hundred clinical trials around the globe2.

Globally, clinical trial registries may be considered the best source to review the ongoing clinical trial scenario as crucial details pertaining to proposed intervention, study type and design, sample size, and outcomes and phase of the trial are publicly available. The Clinical Trials Registry - India (CTRI), one of the primary registries of the World Health Organization's International Clinical Trial Registry Platform (ICTRP), is one such database3,4.

The CTRI, set up under the aegis of the Indian Council of Medical Research (ICMR), is managed by the ICMR-National Institute of Medical Statistics, New Delhi. The CTRI is a free online registry that prospectively registers clinical trials being conducted in India and also in countries which do not have a primary registry of their own. With the emergence of the pandemic in India, there has been a steady increase in the registration of clinical trials on COVID-19 in the CTRI. Here, we present a comprehensive overview of the COVID-19 trials registered in the CTRI (Tables I-IV). While the results of these trials will decide whether or not any of these proposed therapies are likely to be of use, information about these would help to identify lacunae as well as plan and guide future clinical research.

Table I.

An overview of 122 COVID-19 trials registered in the Clinical Trials Registry - India#

Intervention Number Type of trial Participant health condition

Modern medicine (n=42)

Drug (n=28)
Individual drugs 24 Therapeutic efficacy=19
Prophylactic efficacy=5
Healthy volunteers at high risk - 4
Healthy volunteers at moderate/high risk - 1
Mild COVID-19 - 5
Mild-to-moderate COVID-19 - 1
Moderate COVID-19 - 1
Moderate-to-severe COVID-19 - 2
Severe COVID-19 - 4
Severity not specified - 6
Combination drugs 4 Therapeutic efficacy=4 Moderate COVID-19 - 1
Mild, moderate, severe COVID-19 - 1
Non-severe and severe COVID-19 - 1
Severity not specified - 1
Phytopharmaceutical (n=2)
Phytopharmaceutical 2 Therapeutic efficacy=2 Asymptomatic/mild COVID-19 - 1
Moderate COVID-19 - 1
Cell- and plasma-based therapies (n=9)
Cell- and plasma-based therapies 9 Therapeutic efficacy=9 Moderate COVID-19 - 1
Moderate-to-severe COVID-19 - 1
Severe COVID-19 - 5
Severity not specified - 2
Biological products (n=3)
Vaccine 3 Therapeutic efficacy=2
Prophylactic efficacy=1
Healthy volunteers at high risk - 1
Moderate-to-severe COVID-19 - 1
Severe COVID-19 - 1
Traditional medicine (n=67)
Ayurveda (n=45)

Classical individual agents 11 Therapeutic efficacy=1
Prophylactic efficacy=10
Healthy volunteers at high risk - 1
Healthy volunteers in the community - 9
Asymptomatic/mild symptoms - 1
Classical combination preparations* 10 Therapeutic efficacy=4
Prophylactic efficacy=6
Healthy volunteers at high risk - 1
Healthy volunteers in the community - 5
Asymptomatic/mild symptoms - 3
Mild-to-moderate COVID-19 - 1
Patented products 24 Therapeutic efficacy=18
Prophylactic efficacy=6
Healthy volunteers at high risk - 5
Healthy volunteers in the community - 1
Asymptomatic/mild symptoms - 3
Asymptomatic/mild/moderate symptoms - 2
Mild symptoms - 4
Mild-to-moderate COVID-19 - 6
Moderate COVID-19 - 1
Moderate-to-severe COVID-19 - 1
Severe COVID-19 -1
Yoga (n=3)
Yoga* 3 Therapeutic efficacy=2
Stress management=1
Healthy volunteers at high risk - 1
Asymptomatic/mild symptoms - 1
Asymptomatic/uncomplicated illness/mild pneumonia - 1
Unani (n=2)
Unani 2 Prophylactic efficacy=2 Healthy volunteers at risk - 2
Siddha (n=3)
Siddha 3 Therapeutic efficacy=2
Prophylactic efficacy=1
Healthy volunteers in community and healthcare workers - 1
Asymptomatic - 1
Asymptomatic/mild/moderate symptoms - 1
Homeopathy (n=14)
Homeopathy 14 Therapeutic efficacy=8
Prophylactic efficacy=6
Healthy volunteers in community - 3
Healthy volunteers at high risk - 3
Asymptomatic - 1
Asymptomatic/mild symptoms - 1
Mild - 4
Moderate - 1
Mild/moderate/severe symptoms - 1
Miscellaneous (n=13)
Miscellaneous 13 Therapeutic efficacy=2
Prophylactic efficacy=1
Process-of-care changes=9
Diagnostic=1
Healthy volunteers - 4
Severe COVID-19 - 1
Severity not specified - 4
Other (non-COVID-19) - 4

#Registered trials as on June 5, 2020; *Two Ayurveda classical combination trials included yoga and one yoga trial included Ayurveda interventions. In addition, one Ayurveda trial was in combination with homeopathy and one miscellaneous trial with combination of modern medicine, Ayurveda and homeopathy

Table IV.

Details of miscellaneous trials (n=13) on coronavirus disease 2019 registered in the Clinical Trials Registry - India#

Serial number CTRI number Intervention details Study design Blinding Phase Sample size Primary outcome Sponsor and regulatory status States and UTs
1 CTRI/2020/05/025248 Arm 1: Brief tele-counselling model for coping with psychological concerns associated with COVID-19 Non-randomized, multiple-arm trial N/A N/A 128 Anxiety (assessed as a continuous variable on HADS) PI initiated, MB Hospital RNT Medical College Udaipur DCGI approval: N/A RJ
2 CTRI/2020/05/025492 Arm 1: Tele-consultation
Arm 2: Standard arm with routine follow up visits
Randomized, parallel-group trial Open label N/A 2978 Need for emergency room visit or re-hospitalization JIPMER, Puducherry
DCGI approval: N/A
PY
3 CTRI/2020/05/025331 Arm 1: Home-based prehabilitation Non-randomized, active controlled trial NIL N/A 15 Change in emotional functioning by DASS-21, physical functioning by change in performance score (Karnofsky Performance Scale) score and change in respiratory functional parameters AIIMS, New Delhi
DCGI approval: N/A
DL
4 CTRI/2020/05/024962 Arm 1: Povidone-iodine gargles and intranasal application
Arm 2: Normal saline
Randomized, parallel-group trial N/A N/A 96 Comparing the reduction in the progression, transmission of disease assessed by viral load Win Medicare Pvt Ltd, Vijaywada
DCGI approval: N/A
AP
5 CTRI/2020/05/024983 Arm 1: Topical lignocaine lozenges Single-arm trial N/A N/A 30 Sensitivity of nasal and throat swabs for RT-PCR of COVID-19 after topical lignocaine use AIIMS, New Delhi
DCGI approval: N/A
DL
6 CTRI/2020/04/024776 Arm 1: Chest X-ray artificial intelligence module
Arm 2: CT- scan of thorax AI module
Arm 3: Voice sampling AI module
Arm 4: Normal individuals’ chest X-ray, CT-scan thorax and voice sampling
Non-randomized, multiple-arm trial N/A N/A 1650 Assess sensitivity and specificity of AI module by performing chest X-ray, CT-thorax and voice sampling PI initiated
RNT Medical College, Udaipur
DCGI approval: N/A
RJ (2 sites)
7 CTRI/2020/05/025071 Arm 1: Lowest driving pressure-guided PEEP
Arm 2: Conventional lung protective ventilation strategy
Randomized, parallel-group trial Participant blinded Phase 3 40 Difference in the area under the curve (adjusted to survival time) for Murray’s lung injury score in the first 4 days AIIMS, New Delhi
DCGI approval: N/A
DL
8 CTRI/2020/05/025489 Arm 1: CMAC video laryngoscope
Arm 2: McGrath MAC video laryngoscope
Randomized, parallel-group trial Participant and outcome assessor blinded N/A 60 Time to intubation AIIMS, New Delhi
DCGI approval: N/A
DL
9 CTRI/2020/06/025522 Arm 1: Touren non-channelled video laryngoscope
Arm 2: King Vision channelled video laryngoscope
Randomized, cross-over trial Outcome assessor blinded N/A 50 Time to intubation AIIMS, New Delhi DCGI approval: N/A DL
10 CTRI/2020/06/025589 Arm 1: COVID barrier box with Ambu King vision video laryngoscope
Arm 2: COVID barrier box with Macintosh laryngoscope
Randomized, parallel-group, active controlled trial NIL N/A 60 Intubation time AIIMS, Bhubaneswar DCGI approval: N/A OR
11 CTRI/2020/04/024747 Arm 1: Simulation-based training of ventilatory management of COVID-19 patients Single-arm trial Participant and outcome assessor blinded N/A 26 Prepare a module for non-anaesthesiology trainees to handle ventilators in COVID-19 patients GSL Medical College, Rajahmundry
DCGI approval: N/A
AP
12 CTRI/2020/05/025490* Arm 1: Chlopromazine + NBE extract concoction + cholecalciferol + Azadirachta indica bark extract concoction + Arsenicum album + tea + Arm 2: Standard treatment Randomized parallel-group active controlled trial Participant and investigator blinded Phase 2/3 110 Protection from COVID-19 infection Siddhartha Hospital, Agra
DCGI approval: N/A
UP
13 CTRI/2020/04/024659 Arm 1: Shreepad Shree Vallabh formulation Single-arm trial N/A Phase 3 30 Improvement in symptoms of ambulatory patients which include cough, fever with or without chills and difficulty in breathing SSV Phytopharmaceuticals, Mumbai
DCGI approval: N/A
MH

#Registered trials as on June 5, 2020, *Combination trials with modern medicine, Ayurveda and homeopathy. Table data are as per information provided by trialist. AIIMS, All India Institute of Medical Sciences; COVID-19, coronavirus disease 2019; JIPMER, Jawaharlal Institute of Postgraduate Medical Education and Research; MB Hospital RNT Medical College, Maharana Bhupal Hospital, Ravindra Nath Tagore Medical College; PI, principal investigator; AI, artificial intelligence; DCGI, Drugs Controller General of India; N/A, not applicable; HADS, hospital anxiety and depression scale; DASS-21, depression, anxiety and stress scale 21 items; RT-PCR, reverse transcription-polymerase chain reaction. States and Union Territories (UTs): AP: Andhra Pradesh; AR: Arunachal Pradesh; AS: Assam; BR: Bihar; CG: Chhattisgarh; GA: Goa; GJ: Gujarat; HR: Haryana; HP: Himachal Pradesh; JK: Jammu and Kashmir; JH: Jharkhand; KA: Karnataka; KL: Kerala; MP: Madhya Pradesh; MH: Maharashtra; MN: Manipur; ML: Meghalaya; MZ: Mizoram; N: Nagaland; OR: Odisha; PB: Punjab; RJ: Rajasthan; SK: Sikkim; TN: Tamil Nadu; TR: Tripura; UK: Uttarakhand; UP: Uttar Pradesh; WB: West Bengal; TS: Telangana; AN: Andaman and Nicobar Islands; CH: Chandigarh; DH: Dadra and Nagar Haveli; DD: Daman and Diu; DL: Delhi; LD: Lakshadweep; PY: Puducherry

Trial data extraction

One hundred and twenty three registered COVID-19 trials were extracted from the CTRI database using the term %covid% in the different fields of the CTRI data set. These trials were manually screened and analyzed. One trial was excluded because COVID-19 was in the exclusion criteria in that trial. The remaining 122 trials were tabulated into three categories: modern medicine (including drug trials as well as phytopharmaceuticals, cell- and plasma-based therapies and biological products trials); traditional medicine covering Ayurveda, Yoga and Naturopathy, Unani, Siddha, Homeopathy (AYUSH) trials and miscellaneous trials.

COVID-19 trial scenario in India

Multiple therapeutic and preventive trials including those in the traditional systems of medicine are being conducted in India with the common global objective of demonstrating efficacy as well as safety for all in need. Of the 122 clinical trials on COVID-19 registered in the CTRI (as on June 5, 2020), 42 were on the modern system of medicine, 67 on the traditional system of medicine and 13 miscellaneous (Table I). Overall, there were 23 single-armed trials, 68 randomized trials and six cluster randomized trials, while there were 17 non-randomized and eight other (unspecified study design) trials. Most of these trials were either Phase 2 (n=31) or Phase 2/3 (n=13) trials or Phase 3 (n=23) or Phase 3/4 (n=7) trials. Phase was not applicable for 34 trials, and there were only two Phase 1 and five Phase 1/2 trials (Tables II-IV). Of the remaining trials, four trials were marked as Phase 4 trials and two as post-marketing surveillance studies. There was a wide variation in sample size in the registered trials ranging from 6 to 50,000.

Table II.

Details of modern medicine trials (n=42) on COVID-19 registered in the Clinical Trials Registry - India#

Serial number CTRI number Intervention details Study design Blinding Phase Sample size Primary outcome Sponsor and regulatory status States and UTs

Drug trials (n=28)

Antivirals
1 CTRI/2020/04/024773* Solidarity trial Arm 1: Remdesivir and standard treatment
Arm 2: Chloroquine or HCQ and standard treatment
Arm 3: Lopinavir with ritonavir
Arm 4: Lopinavir with ritonavir plus interferon and standard treatment
Arm 5: Standard treatment
Randomized, parallel-group, multiple-arm trial Open label Phase 3 1500 All-cause mortality, subdivided by the severity of disease at the time of randomization, measured using patient records throughout the study WHO and ICMR, New Delhi DCGI approval: Yes RJ (2 sites), MP (2 sites), DL, TN (5 sites), MH (7 sites), GJ (4 sites), TS, GJ, AP
2 CTRI/2020/06/025575* Arm 1: HCQ, ribavirin, standard treatment (NS)
Arm 2: HCQ, ribavirin, standard treatment (S)
Arm 3: Lopinavir, ritonavir, ribavirin, standard treatment (S)
Arm 4: Standard treatment (NS)
Arm 5: Standard treatment
Randomized, parallel-group, multiple-arm trial Open label Phase 3/Phase 4 175 1. Time to clinical recovery 2. Time to 2019-nCoV RT-PCR negativity in upper respiratory tract specimen AIIMS, Rishikesh DCGI approval: N/A UK
3 CTRI/2020/05/025114 Arm 1: Favipiravir
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 3 150 Time until cessation of oral shedding of SARS-CoV-2 virus (time frame: up to 28 days) (time in days from randomization to a negative SARS-CoV-2 RT-PCR result of both oropharyngeal swab and nasopharyngeal swab) Glenmark Pharmaceuticals Ltd, Mumbai DCGI approval: Yes CG, MH (7 sites), GJ (3 sites), DL
Antimalarials
4 CTRI/2020/04/024479 Arm 1: Chloroquine phosphate
Arm 2: Standard treatment
Randomized, parallel-group trial Open label N/A 32 Number of days of hospitalization Command Hospital Airforce, Bengaluru DCGI approval: N/A KA
5 CTRI/2020/04/024729 Arm 1: Topical chloroquine and standard treatment
Arm 2: Standard treatment
Other Open label Phase 2 60 1. The Ct values on days 0, 3, 7, 10 shall be plotted on a graph for all patients.
2. The rate of decline for each patient shall be calculated. The time to cure (COVID-19 RT PCR -ve) shall be determined.
3. The two groups shall be compared for (i) rate of decline of Ct values; (ii) time to cure; (iii) rate of cure or alternate outcome
AIIMS New Delhi DCGI approval: N/A HR
6 CTRI/2020/03/024402 Arm 1: HCQ
Arm 2: HCQ (ICMR regimen)
Randomized, parallel-group, active controlled trial Open label Phase 3 500 Infected non-infected PI initiated, Aster Malabar Institute of Medical Sciences, Kozikhode DCGI approval: N/A KL
7 CTRI/2020/05/025022 Arm1: HCQ
Arm 2: Standard treatment
Other Open label Phase 2 166 Progression to moderate-to-severe disease AIIMS, New Delhi
DCGI approval: N/A
DL
8 CTRI/2020/05/025067 Arm 1: HCQ along with standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial Open label N/A 6950 Laboratory-confirmed symptomatic COVID-19 cases George Institute for Global Health India, New Delhi DCGI approval: N/A TN, KA, DL
9 CTRI/2020/04/024904* Arm 1: HCQ
Arm 2: HCQ (high dose)
Arm 3: HCQ and Azithromycin
Randomized, parallel group trial Participant and outcome assessor blinded Phase 3 300 1. Death
2. Hospitalized on invasive mechanical ventilation or extracorporeal mechanical ventilation
3. Hospitalized on non-invasive ventilation or high-flow nasal cannula oxygen therapy
4. Hospitalized on supplemental oxygen
5. Hospitalized not on supplemental oxygen
6. Not hospitalized with limitation of activity (due to continued symptoms)
7. Not hospitalized without limitation in activity (no symptoms)
Armed Forces Medical Services, New Delhi DCGI approval: N/A UP (4 sites), DL, GJ
10 CTRI/2020/05/025242 Arm 1: HCQ Other N/A N/A 400 Pharmacokinetics of HCQ ICMR, New Delhi DCGI approval: N/A MH
Immunomodulators
11 CTRI/2020/04/024948* Arm 1: Ciclesonide
Arm 2: HCQ
Arm 3: Ivermectin
Arm 4: Standard treatment
Randomized, parallel-group trial N/A Phase 2 120 Proportion of patients having virologic cure on day 6 in each of the groups Lady Hardinge Medical College, New Delhi DCGI approval: N/A DL
12 CTRI/2020/04/024806 Arm 1: Imatinib
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 100 1. Proportion of patients with negative viral titre on day 7
2. Proportion of patients with negative viral titre on day 14
AIIMS New Delhi DCGI approval: N/A DL
13 CTRI/2020/05/024959 Arm 1: Itolizumab,
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2 30 One-month mortality rate Biocon Biologics India Limited, Bengaluru DCGI approval: Yes DL (3 sites), MH (3 sites), KA
14 CTRI/2020/05/025369 Arm 1: Tocilizumab and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 3 180 Proportion showing progressive COVID-19 disease from moderate to severe, or from severe disease to death Medanta Institute of Education and Research, Gurgaon DCGI approval: Yes TS, TN, MH (3 sites), HR (4 sites) DL, UP (2 sites)
15 CTRI/2020/04/024846 Arm 1: Mycobacterium w and standard treatment
Arm 2: Placebo and standard treatment
Randomized, parallel-group, placebo-controlled trial Participant, investigator and outcome assessor blinded N/A 40 Improvement in organ dysfunction (or occurrence of new organ dysfunction) based on change in SOFA score and ordinal scale Cadila Pharmaceuticals Limited, Ahmedabad DCGI approval: Yes CG, MP, DL, CH
16 CTRI/2020/05/025271 Arm 1: Mycobacterium w and standard treatment
Arm 2: Placebo and standard treatment
Randomized, parallel-group, placebo-controlled trial Participant, investigator and outcome assessor blinded Phase 3 480 Number of patients with increased disease severity Cadila Pharmaceuticals Limited, Ahmedabad DCGI approval: Yes DL, MP, CH
17 CTRI/2020/05/025277 Arm 1: Mycobacterium w
Arm 2: Placebo
Randomized, parallel-group, placebo-controlled trial Participant, investigator and outcome assessor blinded Phase 3 4000 Numder of individuals acquiring COVID-19 infection Cadila Pharmaceuticals Limited, Ahmedabad DCGI approval: Yes MP, CG, DL, CH
18 CTRI/2020/05/025350 Arm 1: Mycobacterium w, (heat killed) Single-arm trial Open label Phase 2 50 Clinical improvement, as defined by live discharge from the hospital, a decrease of at least two points from baseline on a modified ordinal scale. Conversion of COVID-19 status to negative R D Gardi Medical College, Ujjain DCGI approval: N/A MP
19 CTRI/2020/06/025613 Arm 1: Melatonin
Arm 2: Placebo
Randomized, parallel-group, placebo-controlled trial Participant and investigator blinded Phase 4 200 SARS-CoV-2 infection rate PI initiated, AIIMS Rishikesh
DCGI approval: N/A
UK
Anthelmintics
20 CTRI/2020/04/024858 Arm 1: Ivermectin and standard treatment
Arm 2: Standard treatment
Non-randomized, active controlled trial Open label N/A 50 Confirm the antivirus effectiveness of ivermectin on coronavirus i.e., COVID-19 then to explore its potential use in the combating to the COVID-19 pandemic Max Super Speciality Hospital, New Delhi DCGI approval: N/A DL
21 CTRI/2020/05/025068 Arm 1: Ivermectin
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label 50 Reduction in the viral load in patients with haematological illnesses who are admitted with COVID-19 infection Christian Medical College, Vellore DCGI approval: N/A TN
22 CTRI/2020/05/025224 Arm 1: Ivermectin, and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 50 Effect of ivermectin on eradication of virus. Test for virus at 1, 3 and 5 days from beginning of trial drug started for the patient in the hospital RD Gardi Medical College, Ujjain DCGI approval: N/A MP
23 CTRI/2020/05/025333 Arm 1: Ivermectin
Arm 2: No intervention
Randomized, parallel-group trial Open label Phase 2 2000 1. Resolution of sign and symptoms of COVID-19
2. Negative RT-PCR done 48 h after ivermectin dose
3. Change/reduction in Ct value as reported in RT-PCR for SARS-CoV-2 virus assay
R D Gardi Medical College, Ujjain DCGI approval: N/A MP
24 CTRI/2020/04/024949 Arm 1: Niclosamide
Arm 2: Standard treatment
Randomized, parallel-group trial N/A Phase 2 48 Proportion of patients having virologic cure on day 6 Lady Hardinge Medical College, New Delhi DCGI approval: N/A DL
Antihypertensive
25 CTRI/2020/05/025319 Arm 1: Losartan Arm 2: Placebo Randomized, parallel-group, placebo-controlled trial Participant and investigator blinded Phase 3 186 Percentage of patient with treatment failure: (i) fall in 1 score in Respiratory SOFA score; (ii) new requirement of respiratory assist devices (HFNC, NIV); (iii) new requirement of mechanical ventilation; (iv) mortality SGPGI, Lucknow DCGI approval: N/A UP
Antioxidant/pro-oxidant
26 CTRI/2020/05/025336 Arm 1: Resveratrol-copper and standard treatment
Arm 2: Sodium-copper- chlorophyllin and standard treatment
Arm 3: Standard treatment
Randomized, parallel-group, multiple-arm trial Open label Phase 3 300 Proportion of patients who suffer clinical deterioration OR viral persistence at day 10 from the date of randomization (excluding the date of randomization) Tata Memorial Centre, Mumbai DCGI approval: N/A MH
27 CTRI/2020/05/025337 Arm 1: Resveratrol-copper tablets, and standard treatment
Arm 2: Sodium-copper- chlorophyllin and standard treatment
Arm 3: Standard treatment
Randomized, parallel-group, multiple-arm trial Open label Phase 2 200 Time to clinical improvement, defined as a 2-point improvement on a 7-point ordinal scale Tata Memorial Centre, Mumbai DCGI approval: N/A MH
Antineoplastic
28 CTRI/2020/06/025664 Arm 1: 2-deoxy-D-glucose and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2 40 Time to clinical improvement Dr Reddys Laboratories Limited, Hyderabad and INMAS, DRDO, Delhi DCGI approval: Yes DL (2 sites), KA, TN, UP (2 sites), MH (4 sites), AP, GJ Phytopharmaceuticals (n=2)
29 CTRI/2020/05/025397 Arm 1: Purified AQCH and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 210 Proportion of patients showing clinical improvement.
Clinical improvement defined as patient meeting discharge criteria OR a 2-point improvement (from time of enrolment) in disease severity rating on the 7-point ordinal scale
Sun Pharmaceutical Industries Limited, Goregaon, Mumbai DCGI approval: Yes CG, MH (6 sites), MP, TS, UP, HR, JK, DL, TN
30 CTRI/2020/05/025167 Arm 1: Thymoquinone and standard treatment
Arm 2: Standard treatment
Non-randomized active controlled trial Open label Phase 2 100 Characterize virologic and clinical response Intas Pharmaceuticals Ltd, Ahmedabad DCGI approval: N/A GJ (3 sites)
Cell and plasma based therapies (n=9)
31 CTRI/2020/04/024775 PLACID trial Arm 1: Convalescent plasma
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial N/A Phase 2 452 Composite measure of the avoidance of : (i) progression to severe ARDS (P/F ratio 100) or (ii) all-cause mortality at 28 days ICMR, New Delhi DCGI approval: Yes MH (7 sites), BR, MP (3 sites), TS (2 sites) GJ (6 sites), KA (4 sites), PY, UP (4 sites), DL, TN (5 sites), HR, CH, PB, RJ (2 sites)
32 CTRI/2020/04/024706 Arm 1: Convalescent plasma and standard treatment
Arm 2: Random donor plasma and standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2 40 Proportion of patients remaining free of mechanical ventilation in both groups Institute of Liver and Biliary Sciences, New Delhi DCGI approval: Yes DL (2 sites)
33 CTRI/2020/04/024915 Arm 1: Convalescent plasma
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 100 The primary outcome was a composite measure of the avoidance of : (i) progression to severe ARDS (P/F ratio 100) and (ii) all-cause mortality at 28 days Max Super Speciality Hospital, New Delhi DCGI approval: Yes DL
34 CTRI/2020/04/024804 Arm 1: Convalescent plasma along with standard treatment
Arm 2: Standard treatment
Non-randomized, active controlled trial N/A Phase 1/2 24 Safety, efficacy, side effects measured by chest radiograph. Improvement of clinical symptoms including duration of fever, respiratory distress, pneumonia, cough, sneezing, and diarrhoea within three days of the convalescent plasma transfusion International Stemcell Services Ltd, Bengaluru DCGI approval: Yes KA (2 sites)
35 CTRI/2020/05/025299 Arm 1: Convalescent plasma
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 20 Avoidance of progression to severe ARDS Wockhardt Ltd, Mumbai
DCGI approval: Yes
MH
36 CTRI/2020/05/025346 Arm 1: Convalescent plasma and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial N/A N/A 90 Progression to severe ARDS (P/F ratio 100) and all-cause mortality at one month Government of Tamil Nadu
DCGI approval: Yes
TN
37 CTRI/2020/05/025328 Arm 1: Convalescent plasma
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial N/A Phase 2 100 Composite measure of the (i) all-cause mortality at 28 days; (ii) improvement of SOFA score post transfusion Apollo Hospitals Enterprise Limited, New Delhi DCGI approval: Yes WB, TS, MH, TN, DL
38 CTRI/2020/05/025209 Arm 1: Convalescent plasma
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 2 80 1. All-cause mortality
2. To identify the immune correlates for response to plasma therapy
CSIR, New Delhi DCGI approval: Yes WB
39 CTRI/2020/05/025432 Arm 1: Cytokine cocktail therapy Single-arm Trial Open label Phase 1 6 Safety of cytokine cocktail therapy International Stemcell Services Ltd, Bengaluru DCGI approval: Yes KA

Biological products (n=3)

Vaccines

40 CTRI/2020/04/024749 Arm 1: Recombinant BCG vaccine - VPM1002
Arm 2: Placebo
Randomized, parallel-group, placebo controlled trial Participant, investigator, outcome assessor and date-entry operator blinded Phase 3 5946 1. Number of individuals with laboratory-confirmed COVID-19 infection
2. Number of individuals with laboratory-confirmed COVID-19 infection among other high risk individuals
3. Number of laboratory-confirmed COVID-19 infection with severe, critical or life-threatening disease as assessed by investigator among HCWs
4. Number of laboratory-confirmed COVID-19 infection with severe, critical or life-threatening disease as assessed by investigator among other high-risk individuals
Serum Institute of India Pvt Ltd, Pune DCGI approval: Yes OR, CG, MH (17 sites), DL (4 sites), GA, KL, AP, UP, WB, CH, HR, RJ, GJ, TN, KA (2 sites)
41 CTRI/2020/04/024833 Arm 1: BCG-Denmark (Green Signal)
Arm 2: Placebo
Randomized, parallel-group, placebo controlled trial Participant, investigator, outcome assessor and date-entry operator blinded N/A 1826 Proportion of HCW with symptomatic COVID-19 disease PI initiated, JIPMER, Puducherry DCGI approval: N/A PY
42 CTRI/2020/05/025013 Arm 1: BCG
Arm 2: Saline plus standard treatment
Non-randomized, active controlled trial Participant blinded Phase 2 60 1. Total duration of hospitalization with COVID-19 symptoms
2. Decrease in viral titre
3. Duration of COVID-19 symptoms
Medical Education and Drugs Department, Mumbai DCGI approval: Yes MH

#Registered trials as on June 5, 2020, *Combination therapy trials are mentioned in only one category to avoid duplication. Table data are as per information provided by trialist. The keyword ‘Standard treatment’ has been used for uniformity and includes the following category as mentioned by the trialist i.e., standard of care, standard care of treatment and supportive management, standard treatment protocol, local-level standard treatment, best supportive care and treatment guidelines as per MoHFW. COVID-19, coronavirus disease 2019; AIIMS, All India Institute of Medical Sciences; ICMR, Indian Council of Medical Research, INMAS, Institute of Nuclear Medicine and Allied Sciences; DRDO, Defence Research and Development Organisation; HCQ, Hydroxychloroquine; R D Gardi Medical College, Ruxmaniben Deepchand Gardi Medical College; SGPGI, Sanjay Gandhi Postgraduate Institute of Medical Sciences; CSIR, Council of Scientific and Industrial Research; WHO, World Health Organization. PI, Principal investigator; N/A, not applicable; AQCH, aqueous extract of Cocculus hirsutus; CTRI, Clinical Trials Registry - India; HCQ, healthcare workers; RT-PCR, reverse transcription-polymerase chain reaction; SOFA, sequential organ failure assessment; NS, non-severe; S, severe; Ct, cycle threshold. States and Union Territories (UTs): AP: Andhra Pradesh; AR: Arunachal Pradesh; AS: Assam; BR: Bihar; CG: Chhattisgarh; GA: Goa; GJ: Gujarat; HR: Haryana; HP: Himachal Pradesh; JK: Jammu and Kashmir; JH: Jharkhand; KA: Karnataka; KL: Kerala; MP: Madhya Pradesh; MH: Maharashtra; MN: Manipur; ML: Meghalaya; MZ: Mizoram; N: Nagaland; OR: Odisha; PB: Punjab; RJ: Rajasthan; SK: Sikkim; TN: Tamil Nadu; TR: Tripura; UK: Uttarakhand; UP: Uttar Pradesh; WB: West Bengal; TS: Telangana; AN: Andaman and Nicobar Islands; CH: Chandigarh; DH: Dadra and Nagar Haveli; DD: Daman and Diu; DL: Delhi; LD: Lakshadweep; PY: Puducherry

Modern medicine

Trials registered in this category (n=42) are subdivided into drug trials (n=28), of which 24 trials are on individual drugs which primarily evaluate their therapeutic efficacy (n=19) as do all of the four combination of drug trials (such as the global Solidarity trial). These trials are being conducted in patients with varying severity of COVID-19 ranging from mild to moderate to severe. The severity of COVID-19 has not been specified in seven of these drug trials (Table I). Others include trials on phytopharmaceuticals (n=2) cell- and plasma-based therapies (n=9) and biological products (n=3). Only one of these is a prophylactic trial on healthy volunteers and all cell- and plasma-based therapy trials are on either moderate/moderate to severe or severe (n=5) COVID-19 patients. While the key features of these registered trials are presented in Table II, these are briefly discussed below.

Drug trials

Antivirals

Solidarity trial: The Solidarity trial is an international clinical trial initiated by the WHO to help find an effective treatment for COVID-195. The trial compares four treatment options remdesivir; lopinavir/ritonavir; lopinavir/ritonavir with interferon beta-1a and chloroquine or hydroxychloroquine (HCQ) against standard of care, to assess their relative effectiveness against COVID-19. The Solidarity trial has been planned as an open-labelled, randomized, parallel-group, multiple-arm trial with a total sample size of 7000 participants, of whom 1500 participants are to be enrolled from India from 24 sites. The trial is being conducted in India with the support of ICMR.

In addition, a single-centre trial is also underway to assess the safety and efficacy of antiviral combination therapy such as lopinavir–ritonavir combination and HCQ with ribavirin in severe COVID-19-infected patients (CTRI/2020/06/025575).

Favipiravir: A nucleoside precursor, favipiravir, inhibits the influenza virus as well as a number of other RNA viruses6. In keeping with global trends, a randomized, open-label, multicentre study to evaluate the efficacy and safety of favipiravir in addition to standard supportive care in patients with mild-to-moderate COVID-19 is currently underway at 12 sites across India (CTRI/2020/05/025114).

Antimalarials

During this pandemic time, chloroquine and HCQ have generated much interest in the global community as potential therapeutic agents against COVID-197. An open-label non-randomized trial showed that HCQ - azithromycin was associated with viral load reduction in COVID-19 patients8.

Chloroquine: Two open-labelled, randomized controlled trials are being conducted to determine the efficacy of chloroquine in COVID-19 patients who present with severe acute respiratory illness (CTRI/2020/04/024479, CTRI/2020/04/024729).

Hydroxychloroquine (HCQ): In India, the ICMR has proposed a prophylactic dosing schedule of HCQ for healthcare workers9. In this regard, a principal investigator (PI)-initiated trial on 500 participants is currently underway wherein the recommended prophylactic dosing regimen is being compared with an alternative dosing pattern for the prevention of new infection and adverse outcomes in those at high risk of infection (CTRI/2020/03/024402). A double-blind, Phase 3 clinical trial, sponsored by the Armed Forces Medical Services, aims to evaluate the efficacy of two different doses of HCQ and also to compare the efficacy of HCQ with or without azithromycin in mild, moderate and severe COVID-19-infected patients. This trial is being conducted at six sites across the country with 300 participants.

In view of the large-scale use of HCQ in India, a study to document the pharmacokinetics of HCQ in the Indian population has also been registered (CTRI/2020/05/025242). In addition, with respect to the growing body of scientific data, regarding risks associated with the use of HCQ, particularly QTc prolongation and cardiac arrhythmias7, a Phase 2 trial is underway to assess the effect of topical i.e., nasal application of chloroquine in early-stage COVID-19 on viral load and cure rates (CTRI/2020/04/024729).

Immunomodulators

Ciclesonide: A Phase 2 trial being conducted at a government medical college in New Delhi plans to evaluate not only the effects of HCQ but also that of ciclesonide, a glucocorticoid, and ivermectin, an anthelmintic drug, in 120 patients with moderate COVID-19 infection (CTRI/2020/04/024948).

Imatinib: Imatinib, which inhibits BCR - ABL tyrosine kinase, revolutionized the treatment of chronic myelogenous leukaemia10. Imatinib has been reported to significantly reduce titres of SARS-CoV and Middle East respiratory syndrome (MERS)-CoV, which depend on ABL kinase activity to fuse and enter into the cells11,12. An open-label, randomized, parallel-group Phase 2 trial with imatinib in 100 patients with mild COVID-19 has been registered in the CTRI (CTRI/2020/04/024806).

Itolizumab: This is an anti-CD6 humanized monoclonal IgG1 antibody which acts upstream by inhibiting the co-stimulation of T cells, resulting in decreased release of signature cytokines of Th1 and Th17 cells13,14. Sponsored by an Indian pharmaceutical company, this open-label, Phase 2, randomized, parallel-group, active controlled multicenter trial is being conducted on 30 patients with moderate-to-severe COVID-19 to assess mortality rates and possible effects on the dreaded cytokine release syndrome (CTRI/2020/05/024959).

Tocilizumab: Interleukin-6 (IL-6) is believed to play an important role in this syndrome, and an IL-6 receptor blocker, tocilizumab, has generated global interest as a potential agent for patients with severe COVID-1915. A multicentric, randomized, Phase 3 trial to evaluate the clinical outcomes and safety of tocilizumab along with standard of care in patients with cytokine release syndrome associated with moderate-to-severe COVID-19 infection has been registered in the CTRI (CTRI/2020/05/025369).

Mycobacterium w: It is a saprophytic cultivable mycobacterium which is a potent immunomodulator. When used as an adjuvant to multidrug therapy, it has been reported to have significant benefits in patients with tuberculosis, leprosy and HIV-AIDS16,17. Three industry-sponsored trials are proposed to be undertaken with this agent in 40 critically ill COVID-19 patients, 480 hospitalized but not critically ill patients as well as 4000 individuals at high risk of contracting the disease. In addition, a Phase 2 observational study with heat killed Mycobacterium w as add-on therapy is also underway on 50 hospitalized COVID-19 patients at a private medical college (CTRI/2020/05/025350).

Melatonin: Melatonin is a remarkably safe and established anti-inflammatory and anti-oxidative molecule with significant evidence suggesting its potential for limiting virus-related diseases, which may extend to COVID-19 as well18. Melatonin has also been reported to possess significant immunomodulatory effects in cancer19. A clinical trial on melatonin is underway to evaluate its role on COVID-19 infection rate along with immune response in high-risk groups after eight weeks of treatment (CTRI/2020/06/025613).

Anthelmintics

Ivermectin: This broad-spectrum antiparasitic agent has been shown to have potent in vitro antiviral activity against a variety of viruses. In in vitro studies, a single dose has been shown to bring a significant reduction in the replication of SARS-CoV-220. This has generated interest in the possibility of repurposing the drug for the management of COVID-19. A total of four clinical trials (CTRI/2020/04/024858, CTRI/2020/05/025068, CTRI/2020/05/025224, CTRI/2020/05/025333) with ivermectin are underway, three of which aim to establish the therapeutic efficacy of ivermectin in COVID-19 patients. The fourth trial is investigating the prophylactic effect of ivermectin on 2000 healthcare workers or healthy contacts (including children) of COVID-19 patients. The primary outcome for this study is resolution of signs and symptoms of COVID-19 and negative reverse transcription-polymerase chain reaction (RT-PCR) done 48 h after drug administration.

Niclosamide: Used to treat tapeworm infestation, niclosamide inhibits ATP production by uncoupling of oxidative phosphorylation. It has been reported to have in vitro antiviral activity21,22. A randomized, parallel-group trial which proposes to investigate the virologic cure rates of niclosamide in patients with mild-to-very mild COVID-19 infection has been registered (CTRI/2020/04/024949).

Antihypertensive

Losartan: Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2 infection and in the process causes internalization and destruction of ACE223. The major complications of COVID-19 are possibly caused by excessive angiotensin II activation due to loss of ACE2 and can be potentially reversed by angiotensin receptor blockers such as losartan24. A randomized, parallel-group, placebo-controlled trial of losartan for the prevention of COVID-19 complications has been registered and is being conducted in an academic setting (CTRI/2020/05/025319).

Antioxidant/pro-oxidant agent

Resveratrol-copper and sodium-copper-chlorophyllin: It has been hypothesized that following microbial infection, cell-free chromatin (cfCh) particles are released from dying cells, causing apoptosis and inflammation in the adjoining host cells. This process triggers a vicious cycle leading to sepsis25. The novel pro-oxidant combination of resveratrol and copper has been reported to inactivate cfCh and demonstrated improved survival in animal models of sepsis26.

The commonly used food colorant and dietary supplement, sodium copper chlorophyllin (SCC), has been reported to have significant antimutagenic and antioxidant properties27. Two trials with resveratrol-copper and SCC as add-on treatment to standard treatment in asymptomatic/mildly symptomatic patients (Phase 3 trial) as well as hospitalized patients (Phase 2 trial) with COVID-19 have been registered (CTRI/2020/05/025336, CTRI/2020/05/025337).

Antineoplastic

2-deoxy-D-glucose (2-DG): A glucose analogue, 2-deoxy-D-glucose, is believed to have profound effects on a range of diseases such as cancer, viral infection and ageing-related morbidity28. Recent in vitro studies suggest the potential benefits of using 2-DG to mitigate COVID-19 infection29,30. A Phase 2 trial to determine the safety and efficacy of the drug as an adjunctive therapy to standard of care in patients with moderate-to-severe COVID-19 is underway at 12 sites (CTRI/2020/06/025664).

Phytopharmaceutical products

Purified aqueous extract of Cocculus hirsutus (AQCH)

An industry-sponsored trial has been registered with aqueous extract of Cocculus hirsutus which is a phytopharmaceutical product derived from the tropical, climbing shrub C. hirsutus. This plant has been reported to have significant medicinal properties in a variety of disease conditions including viral infection31. The trial is proposed to be conducted at 14 sites across the country on patients with moderate COVID-19 (CTRI/2020/05/025397).

Thymoquinone

Nigella sativa, commonly known as black cumin, has shown a wide spectrum of biological activities, the most prominent being antioxidant, anti-inflammatory and antimicrobial activities32. An open-label, two-arm, parallel study is being conducted to evaluate the efficacy and safety of thymoquinone, a phytopharmaceutical compound extracted from Nigella sativa seeds, compared to best supportive care in patients with COVID-19 (CTRI/2020/05/025167).

Cell- and plasma-based therapies

Convalescent plasma therapy (CPT)

For immediate short-term immunity, convalescent plasma therapy (CPT) has generated particular interest as it appears to be safe, to be clinically effective and reduces mortality in times of large-scale epidemics33,34,35. The ICMR has developed a protocol, which is approved by the Drugs Controller General of India, for a multicentre trial (PLACID trial) to test the efficacy of convalescent plasma obtained from recovered COVID-19 patients for administration to moderately ill COVID-19 patients. This is a multicentre, randomized, parallel-group, open-label, active controlled Phase 2 trial to be conducted on 452 patients at 39 sites in India (CTRI/2020/04/024775). In addition, two other trials have been registered which are being conducted by private hospitals on 100 patients each (CTRI/2020/04/024915, CTRI/2020/05/025328). Further, five additional small trials have also been registered investigating the role of CPT in hospitalized severely ill COVID-19 patients (CTRI/2020/04/024706, CTRI/2020/04/024804, CTRI/2020/05/025299, CTRI/2020/05/025346, CTRI/2020/05/025209).

Cytokine cocktail therapy

A Phase 1 trial to evaluate the safety and tolerability of cytokine cocktail therapy in healthy volunteers from healthy donors (derived by T cells) has been registered (CTRI/2020/05/025432). This trial is being conducted at Bengaluru, Karnataka.

Biological products

Vaccines

As per reports, vaccine against COVID-19 is being developed in about 90 institutions worldwide36. Bacille Calmette-Guérin (BCG) is believed to stimulate the general immune response with a consequent faster response to infections that could reduce the severity of disease and lead to quicker recovery rates37. In India, mass immunization with BCG has been underway since 194838. The global interest in BCG was recently sparked when Miller et al39, reported a negative correlation between BCG immunization status of a country and mortalities due to COVID-19. In the CTRI, currently, there are three BCG vaccine trials registered. One of these is on the BCG-Denmark (Green Signal) vaccine for the prevention of COVID-19 in 1826 healthcare workers, whereas the other is a Phase 3 trial of recombinant BCG VPM1002 vaccine for the reduction in infection incidence and severity of COVID-19 in 5946 high risk individuals. Both these trials are triple-blinded, randomized, parallel-group, placebo-controlled trials (CTRI/2020/04/024833 and CTRI/2020/04/024749, respectively). A single-blind, single-centre Phase 2 trial on 60 patients, is evaluating the therapeutic efficacy of BCG in COVID-I9 (CTRI/2020/05/025013).

Traditional medicine

During this pandemic, the potential of traditional medicine is being actively explored through the conduct of clinical trials to identify prophylactic as well as therapeutic agents. The AYUSH approach to manage the outbreak broadly comprises: preventive and prophylactic, symptom management of COVID-19-like illnesses and add-on interventions to the conventional care40. Trials in the AYUSH system of medicine have been registered in the CTRI (n=67) and include Ayurveda (n=45), Yoga and Naturopathy (n=3), Unani (n=2), Siddha (n=3), Homeopathy (n=14) trials (Table III).

Table III.

Details of AYUSH trials (n=67) on coronavirus disease 2019 registered in the Clinical Trials Registry - India#

Serial number CTRI number Intervention details Study design Blinding Phase Sample size Primary outcome Sponsor and regulatory status States and UTs

Ayurveda (n=45)

Classical (n=21)

Individual agents (n=11)
1 CTRI/2020/06/025525 Arm 1: Guduchi Ghana Vati
Arm 2: Nil
Other Open label N/A 20000 Incidence rate of COVID-19 infection IPGTRA, Jamnagar DCGI approval: N/A GJ (5 sites)
2 CTRI/2020/05/025488 Arm 1: Guduchi Ghana Vati
Arm 2: Nil
Randomized, parallel-group trial Open label Phase 2/3 12000 Comparative assessment of incidence of COVID-19 NIA, Jaipur DCGI approval: N/A RJ
3 CTRI/2020/05/025485 Arm 1: Guduchi Ghana Vati
Arm 2: Standard prophylactic care
Non-randomized, active controlled trial Open label Phase 2/3 5000 Comparative assessment of occurrence of COVID-19 infection NIIMH (CCRAS), Hyderabad DCGI approval: N/A TS
4 CTRI/2020/05/025385 Arm 1: Guduchi Ghan Vati
Arm 2: Standard prophylactic care
Non-randomized, multiple-arm trial N/A N/A 40000 Comparative assessment of occurrence of COVID-19 infection CCRAS, New Delhi DCGI approval: N/A WB, PB, TN, KL (2 sites), MH (2 sites), NL, MP, RJ (2 sites), UP, AS, BR (2 sites), KA, HP, GJ (2 sites), AP
5 CTRI/2020/05/025370 Arm 1: Guduchi Ghana Vati Single-arm trial Open label N/A 40 Clinical cure rate: Time to get a negative status of COVID-19 Ayurved University, Jodhpur DCGI approval: N/A RJ (2 sites)
6 CTRI/2020/05/025213 Arm 1: Guduchi Ghana Vati Single-arm trial N/A N/A 1500 Incidence of COVID-19-positive cases as confirmed by RT-PCR CCRAS, New Delhi DCGI approval: N/A HP
7 CTRI/2020/05/025088 Arm 1: Guduchi
Arm 2: Standard prophylactic care
Randomized, parallel-group trial N/A Phase 1/2 1200 Comparative assessment of occurrence of COVID-19 infection in healthy volunteers CCRAS, New Delhi DCGI approval: N/A AP
8 CTRI/2020/05/025429 Arm 1: Ashwagandha + standard prophylactic care
Arm 2: Standard prophylactic care
Non-randomized, active controlled trial Open label Phase 2/3 5000 Comparative assessment of occurrence of COVID-19 infection NIIMH (CCRAS), Hyderabad DCGI approval: N/A TS
9 CTRI/2020/05/025332 Arm 1: Ashwagandha
Arm 2: HCQ
Randomized, parallel-group, active controlled trial Open label Phase 2 400 (i) Proportion of SARS- CoV-2 infection-free participants on completion of study
(ii) Proportion of participants contracting COVID-19 during the study period
Ministry of AYUSH; CSIR, New Delhi DCGI approval: N/A MH
10 CTRI/2020/05/025166 Arm 1: Ashwagandha Randomized, parallel-group trial Open label Phase 2/3 1200 Comparative assessment of occurrence of COVID-19 infection Ministry of AYUSH, New Delhi DCGI approval: N/A AP
11 CTRI/2020/05/025093 Arm 1: Yashtimadhu Other N/A Phase 2/3 1200 Comparative assessment of occurrence of COVID-19 infection Ministry of AYUSH, New Delhi DCGI approval: N/A AP
Combination interventions (n=10)
12 CTRI/2020/05/025171 Arm 1: Guduchi Ghana Vati
2.Anu taila
3.Rock salt and turmeric
4. Ayush preventive guidelines
Arm 2: Standard prophylactic care
Randomized, parallel-group trial Open label Phase 2 50000 Improvement in bala of an individual
Immuno-stimulation leading to non-development of symptoms of COVID-19 in risk population exposed to infected individuals (Bala will be assessed by using specialized proforma including dasvidhapareeksha and other questionnaires which will reveal the physical and mental health of an individual)
AIIA, New Delhi DCGI approval: N/A DL
13 CTRI/2020/05/025069 Arm 1: Guduchi Ghana Vati (Sanshamani Vati) or Sudarshana Ghanavati or Ashwagandha Single-arm trial Open label Phase 3/4 1324 Incidence of COVID-19- positive cases (as confirmed by RT-PCR) CCRAS, New Delhi DCGI approval: N/A DL (3 sites)
14 CTRI/2020/05/025482 Arm 1: Curcumin with black pepper
Arm 2: Standard treatment
Randomized, parallel-group trial Investigator blinded N/A 50 COVID-19 test and acute phase reactants such as D-dimer, CRP, LDH, CBC, ferritin, troponin, cardiac myoglobin, PT INR and appearance of respiratory symptoms Siddhivinayak Pain Relief Center, Pune DCGI approval: N/A MH
15 CTRI/2020/06/025637 Arm 1: Piper betel with the combination of swarnabhasma (herbomineral combination) Cluster randomized trial Participant and investigator blinded N/A 10 Complete blood picture, serum ferritin, C-reactive protein, LDH, troponin, nucleic acid amplification test and RT-PCR ABVGMC, Vidisha DCGI approval: N/A MP
16 CTRI/2020/05/025341* Arm 1: Kiratiktadi Kwath; Ashwagandha churna; Yoga exercises; immunobooster Ayush Kwath
Arm 2: Standard treatment
Randomized, parallel-group trial N/A N/A 30 Efficacy in the management of mild and asymptomatic cases of COVID-19 patients GS Ayurveda Medical College and Hospital, Ghaziabad DCGI approval: N/A UP
17 CTRI/2020/04/024731* Arm 1: Samshamani Vati, Sudarshan Ghana Vati, Khadiradi Vati, Murrchhita Tila Taila (for Nasya, Arsenic Album 30 Single-arm trial Open label Phase 3 50 Episodes and severity of symptoms of respiratory tract infection (cold, sore throat, dry cough, breathlessness) Parul Institute of Ayurved, Vadodara DCGI approval: N/A GJ
18 CTRI/2020/04/024882 Arm 1: Kashaya (decoction) of Tinospora cordifolia stem Piper longum fruit, and standard treatment
Arm 2: Standard treatment
Non-randomized, active controlled trial N/A Phase 3 60 1. Percentage of patients progressing to serious/critical stage of disease
2. Progress of disease as per clinical severity score (COCSS)
3. Number of days of treatment, hospitalization, type of care and site of treatment at hospital, oxygen support requirement, days of ventilation required, period of convalescence and return to normal life activity
4. Number of days taken to test negative for COVID, total days to discharge from hospital
5. Profiling according to tridosha
6. Defining the disease according to Ayurveda
Ministry Of AYUSH, New Delhi DCGI approval: N/A HR
19 CTRI/2020/05/025178 Arm 1: Tab Samshamani Vati; Herbal tea; application of Anu taila; Haridra khanda
Arm 2: Standard prophylactic care
Randomized, parallel-group trial Open label Phase 2 140 Improvement in bala of an individual Bala will be assessed by using specialised proforma including dashavidhapareeksha and other questionnaires which will reveal the physical and mental health of an individual AIIA, New Delhi DCGI approval: N/A DL
20 CTRI/2020/05/025276 Arm 1: Sanshamani Vati (Tinospora cordifolia); Nagaradi kwath (decoction of Zingiber officinale, Terminalia chebula and Tinospora cordifolia); Amalaki Churna (powder of Phyllanthus emblica); Golden Milk (milk with Curcuma longa) Single-arm trial N/A Phase 3 50 Time taken and number of patients progressing from asymptomatic to symptomatic condition Ch Brahm Prakash Ayurved Charak Sansthan, New Delhi DCGI approval: N/A DL
21 CTRI/2020/05/025398* Arm 1: Kiratiktadi Kwath (Astadashang Kwath) Sharangdhar Samhita -kwath prakaran; Ashwgandhachurna with milk; Yoga Single-arm trial N/A N/A 30 1. Efficacy in boosting Vyadhikshamatwa and prevention against communicable diseases.
2. Will help in overcoming the anxiety level and stress of HCQs
GS Ayurveda Medical College and Hospital, Hapur DCGI approval: N/A UP
Patented products (n=24)
22 CTRI/2020/06/025557 Arm 1: AYUSH-64 as add on to standard treatment
Arm 2: Yashtimadhu as add on to standard treatment
Arm 3. Sanshamani Vati Plus; as add-on standard treatment
Arm 4: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2 420 1. Mean time (days) for clinical recovery
2. Proportion of patients showing clinical recovery
Ministry of AYUSH, New Delhi DCGI approval: N/A MH
Patented products (n=24)
23 CTRI/2020/05/025156 Arm 1: AYUSH-64
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 3/4 60 Clinical cure rate: Time to negative conversion of SARS-CoV-2 CCRAS, New Delhi DCGI approval: N/A MH
24 CTRI/2020/05/025335 Arm 1: AYUSH-64 Single-arm trial N/A Phase 3 40 1. Mean time (days) for clinical recovery as per defined clinical recovery criteria
2. Number of patients showing ‘clinical recovery’
CCRAS, New Delhi DCGI approval: N/A DL
25 CTRI/2020/05/025338 Arm 1: AYUSH-64 Single-arm trial N/A Phase 2/3 40 1. Mean time (days) for clinical recovery as per defined clinical recovery criteria
2. Number of patients showing ‘clinical recovery’
CCRAS, New Delhi DCGI approval: N/A DL
26 CTRI/2020/05/025214 Arm 1: AYUSH-64
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2/3 80 1. Mean time (days) for clinical recovery (day of randomization to the day of clinical recovery)
2. Proportion of patients showing ‘clinical recovery’
CCRAS, New Delhi
DCGI approval: N/A
CH
27 CTRI/2020/05/025484 Arm 1: Chyawanprash
Arm 2: Standard prophylactic care
Non-randomized, active controlled trial Open label Phase 2/3 5000 Comparative assessment of occurrence of COVID-19 infection NIIMH (CCRAS), Hyderabad DCGI approval: N/A TS
28 CTRI/2020/05/025425 Arm 1: Chyawanprash Single-arm trial N/A Phase 3/4 50 Percentage of participants with SARS CoV-2 positivity as estimated by RT-PCR of nasopharyngeal swab CCRAS, New Delhi DCGI approval: N/A DL
29 CTRI/2020/05/024981 Arm 1: Chyawanprash with milk
Arm 2: Milk
Randomized, parallel-group trial Open label N/A 600 1. Comparative assessment of incidence of COVID-19
2. Comparative assessment of incidence of other non-COVID-19 infections
Dabur India Ltd, Ghaziabad DCGI approval: N/A GJ (2 sites), MH (2 sites), RJ
30 CTRI/2020/05/025275 Arm 1: Chyawanprash
Arm 2: Standard prophylactic care
Randomized, parallel-group trial N/A Phase 3 200 Percentage of participants with SARS CoV-2 positivity as estimated by RT-PCR CCRAS, New Delhi
DCGI approval: N/A
DL
31 CTRI/2020/06/025592 Arm 1: Shakti drops; turmeric plus; Tulsi arka Single-arm trial Open label Phase 3/4 50 Recovery in the signs and symptoms as fever and respiratory distress Sri Sri Tattva, Bangalore DCGI approval: N/A KA
32 CTRI/2020/06/025590 Arm 1: Astha-15 capsule and standard treatment
Arm 2: Placebo and standard treatment
Randomized, parallel-group, placebo-controlled trial Participant, investigator and outcome assessor blinded Phase 3 120 1. Changes in scores of the St. George Respiratory Questionnaire from baseline to EOT visit
2. Changes in scores of the Leicester Cough Questionnaire from baseline to EOT visit
Dalmia Centre for Research and Development, Noida DCGI approval: N/A AP, RJ, DL, MH
33 CTRI/2020/05/025483 Arm 1: Clevira tablet
Arm 2: Standard treatment
Randomized, parallel-group trial N/A Phase 3/4 100 1. Time taken for clinical recovery, which is defined as: (i) normalization of pyrexia and body pain; (ii) respiratory rate <24/minute; (iii) SpO2 rate >94%; (iv) relief from cough and maintenance of above for > 72 h
2. Proportion of patients with swabs negative for COVID-19 in RT-PCR at day 5, 10 and 15
Apex Laboratories Pvt Ltd, Chennai DCGI approval: N/A TN
34 CTRI/2020/05/025334 Arm 1: SUVED + Reimmungen Single-arm trial N/A Phase 2 30 Prevention of onset or complications of COVID infection Health Solutions, Pune DCGI approval: N/A MH
35 CTRI/2020/05/025343 Arm 1: SUVED + Reimmungen Single-arm trial N/A Phase 2/3 30 Mortality Health Solutions, Pune DCGI approval: N/A MH
36 CTRI/2020/05/025340 Arm 1: ShatPlus and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial Open label Phase 1/2 60 1. Number of days for negative PCR confirmatory test from nasopharyngeal swab for SARS-CoV-2
2. Serum levels of CD4, CD8, NK cell panel CD16/CD56, CRP, IgM, IgG
BVG Life Sciences Ltd, Pune DCGI approval: N/A MH
37 CTRI/2020/05/025161 Arm 1: Aayudh advance bacteria, viruses
Arm 2: Standard treatment
Randomized, parallel-group, active controlled trial Open label Phase 2 120 1. Rate of recovery
2. Symptom resolution: fever
3. Symptom resolution: cough
4. Symptom resolution: shortness of breath
Shukla Ashar Impex Pvt Ltd, Rajkot DCGI approval: N/A GJ
38 CTRI/2020/04/024883 Arm 1: ZingiVir H
Arm 2: N/A
Other Outcome assessor blinded Phase 4 112 The odds of ratio for improvement on a 7-point ordinal scale on day 15 Each day, the worst score from the previous day will be recorded Pankajakasthuri Herbal Research Foundation, Thiruvananthapuram DCGI approval: N/A KA (2 sites), MH
39 CTRI/2020/05/024967 Arm 1: MyVir tablets
Arm 2: Standard treatment
Single-arm trial N/A Post marketing surveillance 30 Improvement in patients who are assessed daily for symptoms which include cough, fever with or without chills and difficulty in breathing for the period they are in quarantine Mi Lab LifeSciences Pvt Ltd, Bengaluru, DCGI approval: N/A KA
40 CTRI/2020/06/025527 Arm 1: Amrta Karuna syrup
Arm 2: Standard treatment
Non-randomized, active controlled trial N/A Post marketing surveillance 30 1. Improvement in patients who are assessed daily for symptoms which include cough, fever with or without chills and difficulty in breathing Vopec Pharmaceuticals Pvt Ltd, Chennai DCGI approval: N/A KA
41 CTRI/2020/05/025326 Arm 1: Tab Pinak Single-arm trial N/A Phase 2 30 Early recovery and reduced mortality Shree Bharadi Ayurvedic, Maharashtra DCGI approval: N/A MH
42 CTRI/2020/05/025273 Arm 1: Tablet pure Ashwagandha 500 mg; Pure Giloy extract; tablet pure tulsi extract; Anu Taila; Swasari Ras
Arm 2: Placebo therapy
Randomized, parallel-group, placebo- controlled trial NIL N/A 120 Virological clearance as measured by RT-PCR of nasopharyngeal swab Patanjali Research Institute, Haridwar; NIMS, Jaipur DCGI approval: N/A RJ
43 CTRI/2020/05/025222 Arm 1: AOIM - Z Tablet Single-arm trial N/A Phase 4 275 Prevention of incidence of COVID-19 infection Shree Dhootapapeshwar Limited, Mumbai DCGI approval: N/A MH
44 CTRI/2020/05/025434 Arm 1: Zingivir-H Randomized, parallel-group, placebo- controlled trial Outcome assessor blinded Phase 4 135 The odds of ratio for improvement on a 7-point ordinal scale on day 15 and clearance of medically attended lung infection due to RT-PCR confirmed COVID-19 infection Pankajakasthuri Herbal Research Foundation, Thiruvananthapuram DCGI approval: N/A KA (2 sites), MH
45 CTRI/2020/06/025556 Arm 1: Virulina
Arm 2: Standard treatment
Randomized, parallel-group, placebo- controlled trial Participant and investigator blinded N/A 30 1. Time to a negative SARS-CoV-2 RT-PCR result of both oropharyngeal swab and nasopharyngeal swab.
2. Clinical cure based on clinician’s assessment of symptoms
a. Change in positive COVID-19 status on day 8 and day 15
3. Clinical outcomes
a. Proportion of patients on WHO progression scale 0 to 10 on day 8 and day 15
Natural Solutions, Mumbai DCGI approval: N/A AP
Yoga and Naturopathy (n=3)
46 CTRI/2020/06/025523 Arm 1: Meditation and breathing exercises and standard treatment
Arm 2: Standard treatment
Randomized, parallel-group trial N/A N/A 84 Depression, anxiety and stress levels in patients assessed using DASS-21 questionnaire National Cancer Institute, Jhajjar DCGI approval: N/A DCGI approval: N/A HR
47 CTRI/2020/05/025162 Arm 1: Alternate nostril breathing and guided meditation; (1) Nadi Shodhan Pranayama; (2) Panchakosha meditation
Arm 2: The control group will not receive the intervention.
Randomized, parallel-group trial N/A N/A 200 PSQI for sleep quality JIPMER, Puducherry DCGI approval: N/A PY
48 CTRI/2020/05/025320* Arm 1: Yoga and Naturopathy, immune-boosting agents such as ginger Tulsi pepper, Adhimaduram, turmeric, gargling, steam inhalation, Sun bath aromatherapy
Arm 2: Standard treatment
Nonrandomized, active controlled trial N/A Phase 3/4 658 Time to progress to next stage of severity i.e., from asymptomatic/uncomplicated/mild pneumonia to moderate/severe stages Government Yoga And Naturopathy Medical College, Chennai DCGI approval: N/A TN (4 sites)
Unani (n=2)
49 CTRI/2020/06/025650 Arm 1: Joshanda (decoction) of the following: Behidana (Cydonia oblonga), Unnab (Zizyphus jujube), Sapistan (Cordia myxa) and Khameera Marwareed Other Open label Phase 2 4000 1. Incidence of COVID-19 cases
2. Improvement in immune status using ISQ
Ministry of AYUSH, New Delhi DCGI approval: N/A KA
50 CTRI/2020/05/025254 Arm 1: Joshanda (decoction) and Khameera Marwareed
Arm 2: Joshanda (decoction) and Tiryaq e Arba
Arm 3: Standard prophylactic care
Non-randomized, multiple-arm trial N/A Phase 3 40000 1. Incidence of COVID-19 cases
2. Improvement in immune status using ISQ
CCRUM, New Delhi DCGI approval: N/A UP, KA, TS, JK, MH, DL
Siddha (n=3)
51 CTRI/2020/06/025625 Arm 1: Kabasura Kudineer and Bramanandhabairavam
Arm 2: Standard treatment
Other Open label Phase 2 86 Proportion of patients confirmed as negative for SARS-CoV-2 in two consecutive throat/nasal swabs (taken 24 h apart) at day 15/day16 Eminentlabs Business Solutions Pvt Ltd, Chennai DCGI approval: N/A TN
52 CTRI/2020/05/025298 Arm 1: Kabasura Kudineer Nilavembukudineer;
Arm 2: Standard prophylactic care
Non-randomized, active controlled trial N/A N/A 21500 Occurrence of COVID-19 infection CCRS, Chennai; Ministry of AYUSH, New Delhi DCGI approval: N/A TN
53 CTRI/2020/05/025215 Arm 1: Kabasura Kudineer
Arm 2: Vitamin C, zinc supplementation
Randomized, parallel-group trial Open label Phase 1/2 50 Reduction in incidence of clinical symptoms of COVID-19, negative conversion of SARS-CoV-2, reduction in viral load of SARS-CoV-2 at the end of treatment and examine the levels immune markers and inflammatory markers Government Stanley Medical College, Chennai DCGI approval: N/A TN
Homeopathy (n=14)
54 CTRI/2020/06/025530 Arm 1: Aconite 30 + Arsenic album 30 + Allium cepa 30 + Influenzum 30 + Gelsmium 30 + Eupatorium 30 + Echinacia 0 + Thuja 0 Non-randomized, active controlled trial N/A N/A 10000 Number of patients with viral fever/COVID-19 Cancer Aid Society, Lucknow DCGI approval: N/A UP
55 CTRI/2020/05/025491 Arm 1: Arsenic album 30c
Arm 2: Bryonia alba 30c
Arm 3: Camphora 1M
Arm 4: Coronavirus-related nosodes (30c potency);
Arm 5: Matching placebo pills
Cluster randomized trial Participant and outcome assessor blinded Phase 2 1000 Number of patients turning symptomatic Life Force Foundation Trust, Mumbai DCGI approval: N/A MH
56 CTRI/2020/05/025272 Arm 1: Arsenicum album 30
Arm 2: No. 40 size globules medicated with alcohol 90% v/v is used as placebo
Cluster randomized trial Participant and investigator blinded N/A 800 COVID-19 in quarantined persons Government Homeo Dispensary, Kerala Government Homeo Dispensary, Kerala KL
57 CTRI/2020/05/025205 Arm 1: Arsenicum album 30c
Arm 2: No intervention
Cluster randomized trial N/A Phase 2/3 33000 Confirmation of diagnosis for COVID-19 infection based on RT-PCR/end of quarantine period CCRH, New Delhi DCGI approval: N/A TN, DL, AP, TS, RJ, WB, KL, MH, UP, GJ
58 CTRI/2020/05/025049 Arm 1: Arsenic album 30c Cluster randomized trial Open label Phase 2/3 100 Clinical recovery (COVID-19 negative) or death Sai Nidan Homeopathy Clinic, Chhattisgarh DCGI approval: N/A CG
59 CTRI/2020/05/024986 Arm 1: Arsenic album 30c Single-arm trial N/A N/A 10000 Confirmation of diagnosis for COVID-19 infection/end of quarantine period as per standard protocol CCRH, New Delhi DCGI approval: N/A DL
60 CTRI/2020/05/024969 Arm 1: Arsenic album 30c (variable dose potency and frequency) and standard treatment
Arm 2: Placebo and standard treatment
Randomized, parallel-group, placebo-controlled trial Open label Phase 2/3 100 Clinical outcome in terms of recovery of patient or requirement of life support (ventilator)/death Naiminath Homoeopathic Medical College Hospital and Research Centre, Agra DCGI approval: N/A UP
61 CTRI/2020/04/024926 Arm 1: Arsenic album, Bryonia alba, Gelsemium, Antimonium tartaricum, Crotalus horridus Single-arm trial Participant blinded Phase 3 100 Clinical recovery (COVID-19 negative) or appearance of symptoms requiring conventional treatment Naiminath Homoeopathic Medical College Hospital and Research Centre, Agra DCGI approval: N/A UP
62 CTRI/2020/04/024905 Arm 1: Arsenic album, Bryonia alba, Gelsemium, Antimonium tartaricum, Crotalus horridus
Arm 2: Placebo
Randomized, parallel-group, placebo-controlled trial Participant blinded Phase 3 100 Clinical recovery (COVID-19 negative) or death. Naiminath Homoeopathic Medical College Hospital and Research Centre, Agra DCGI approval: N/A UP
63 CTRI/2020/04/024857 Arm 1: Arsenic album, Camphora, Bryonia alba, Helleborus niger, Justicia adhatoda Cluster randomized trial Open label Phase 1/2 100 Percentage of patient admissions to critical care Welling Healthcare Private Limited, Mumbai DCGI approval: N/A MH
64 CTRI/2020/06/025558 Arm 1: Bryonia alba 30C
Arm 2: Identical placebo
Randomized, parallel-group, placebo-controlled trial Participant and investigator blinded Phase 4 300 Prophylactic effect Aarogya Homoeopathic Medical College and Hospital, Jaipur; Ministry of AYUSH, New Delhi DCGI approval: N/A RJ
65 CTRI/2020/04/024947 Arm 1: Cadamba 200 Randomized, parallel-group, active controlled trial N/A Phase 3 100 Serologically negative blood test for COVID-19 PI initiated, Homeo clinic, Gondia-Maharashtra DCGI approval: N/A MH
66 CTRI/2020/05/025496 Arm 1: CNV01 Single-arm trial Open label Phase 1 10 Safety measure in terms of investigations (PCR) blood parameters Life Force Foundation Trust, Mumbai DCGI approval: N/A MH
67 CTRI/2020/04/024925 Arm 1: Homoeopathic medicine and standard treatment
Arm 2: Placebo and standard treatment
Randomized, parallel-group, placebo-controlled trial Open label Phase 2 100 Clinical recovery of patient or requirement of life support (ventilator)/death Bajaj Auto Ltd, Maharashtra DCGI approval: N/A MH (2 sites)

#Registered trials as on June 5, 2020, *Trials with combination therapy (involving more than one system of AYUSH) are mentioned in only one category to avoid duplication. AYUSH includes Ayurveda, Yoga, Unani, Siddha, Homeopathy trials. Table data are as per information provided by trialist. The keyword ‘Standard treatment’ and has been used for uniformity and includes the following category as mentioned by the trialist i.e., standard of care, standard care of treatment and supportive management, standard treatment protocol, local-level standard treatment, best supportive care, treatment guidelines as per MOHFW. The term ‘Standard prophylactic care’ has been used for uniformity which represents the terminologies used by the trialist for standard preventive measures against COVID-19. AAIA, All India Institute of Ayurveda; ABVGMC, Atal Bihari Vajpayee Government Medical College; AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy; COVID-19, coronavirus disease 2019; CCRAS, Central Council for Research in Ayurvedic Sciences; CCRUM, Central Council for Research in Unani Medicine; CCRS, Central Council for Research in Siddha; CCRH, Central Council for Research in Homoeopathy; CSIR, Council of Scientific and Industrial Research; IPGTRA, Institute for Post Graduate Teaching and Research in Ayurveda; JIPMER, Jawaharlal Institute of Postgraduate Medical Education and Research; NIA, National Institute of Ayurveda; NIIMH (CCRAS), National Institute of Indian Medical Heritage (CCRAS); NIMS, National Institute of Medical Sciences Jaipur; PI, Principal investigator; N/A, not applicable; ISQ, immune status questionnaire; PSQI, Pittsburgh Sleep Quality Index; HCQ, healthcare worker; RT-PCR, reverse transcription polymerase chain reaction; DASS-21, depression, anxiety and stress scale - 21items; DCGI, Drugs Controller General of India; CRP, C-reactive protein; LDH, lactate dehydrogenase; CBC, complete blood count; PT INR, prothrombin time international normalized ratio; NK, natural killer. States and Union Territories (UTs): AP: Andhra Pradesh; AR: Arunachal Pradesh; AS: Assam; BR: Bihar; CG: Chhattisgarh; GA: Goa; GJ: Gujarat; HR: Haryana; HP: Himachal Pradesh; JK: Jammu and Kashmir; JH: Jharkhand; KA: Karnataka; KL: Kerala; MP: Madhya Pradesh; MH: Maharashtra; MN: Manipur; ML: Meghalaya; MZ: Mizoram; N: Nagaland; OR: Odisha; PB: Punjab; RJ: Rajasthan; SK: Sikkim; TN: Tamil Nadu; TR: Tripura; UK: Uttarakhand; UP: Uttar Pradesh; WB: West Bengal; TS: Telangana; AN: Andaman and Nicobar Islands; CH: Chandigarh; DH: Dadra and Nagar Haveli; DD: Daman and Diu; DL: Delhi; LD: Lakshadweep; PY: Puducherry

Ayurveda

Ayurveda is a comprehensive system of medicine that has been practiced in India for >5000 years41. A total of 45 Ayurveda trials (Tables I and III) are currently registered in the CTRI. These are categorized as individual agents (11 trials) or combination preparations (10 trials, of which 3 trials include other systems of AYUSH such as homeopathy and/or yoga) as available under classical interventions. In addition, there are 24 trials registered on patented ayurvedic products. Four major plant products are under investigation, namely Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra and Curcuma longa (only in combination with other agents).

While the classical interventions, individual and combination trials (n=21), are mostly designed to assess their prophylactic efficacy (n=16) in either healthy human volunteers in the community or those at risk (n=16), the trials with patented products (n=24) are primarily investigating the therapeutic efficacy (n=18) in patients ranging from asymptomatic to moderate to severe COVID-19 patients (Table I).

Classical interventions

Guduchi: Tinospora cordifolia, commonly named as Guduchi, is used in a variety of conditions in the traditional Ayurvedic literature42. Guduchi has been reported to possess a range of activities (antipyretic, anti-inflammatory, antioxidant, anti-infective, anti-neoplastic and immuno-modulatory effects) notable in the context of COVID-1943. Currently, in the CTRI, there are seven registered trials investigating the role of only Guduchi, in healthy high risk individuals in the community to test its role as a preventive agent against COVID-19. Four of these are large trials with sample size ranging from 5000 to 40,000 (the latter has 20 sites across India). In addition, there are three trials exploring the effects of Guduchi in combination with other agents. One of these is being conducted on 50,000 police personnel in Delhi (Table III).

Ashwagandha: Withania somnifera (Ashwagandha) is well known for its anti-inflammatory, antitumour, anti-stress, antioxidant, immunomodulatory, hemopoietic and rejuvenating properties44. In addition, it has been demonstrated to inhibit certain RNA viruses45. The role of Ashwagandha in the prevention of COVID-19 is being investigated in three trials registered in the CTRI, one of which is on 5000 high-risk participants (CTRI/2020/05/025429).

Turmeric: The antiviral effects of curcumin, a plant derivative of turmeric, have been demonstrated in in vitro studies, which makes it an antiviral drug candidate46. Evaluation of the effects of curcumin and adjuvants in COVID-19 patients, in terms of changes in acute-phase reactants and clinical outcome, is being evaluated in a randomized, parallel-group trial on 50 patients (CTRI/2020/05/025482). In addition, polyherbal compounds are being investigated for immunomodulatory and antiviral properties and their potential as therapeutic and prophylactic agents.

Patented products

Currently, there are 24 trials registered on patented products including AYUSH-64 patented by Central Council for Research in Ayurvedic Sciences.

AYUSH 64: A multiplant formulation, AYUSH-64, has been demonstrated to be useful in several research studies carried out over several decades to treat febrile infections including malaria and is considered to possess anti-inflammatory and immunomodulatory effects47. One of its components, Glycyrrhiza glabra or Yashtimadhu, has demonstrated potential as a wound-healing, anti-ulcer and anti-inflammatory agent48. In addition, recent studies reveal that Yashtimadhu may interfere with viral entry as well as replication, thereby impacting the severity of infection49. Further, AYUSH-64 along with standard care has been shown to be effective in influenza-like illnesses with potential for better outcomes50. While a community-based clinical study on 1200 healthy but at-risk individuals has been registered in the CTRI to evaluate the preventive role of only Yashtimadhu, there are five trials on the proprietary formulation, AYUSH 64 (Table III).

Chyawanprash: This is an ancient Indian polyherbal formulation prepared according to a traditional Ayurvedic recipe. It consists of about 50 different medicinal herbs including Emblica officinalis (Indian gooseberry or Amla), a rich source of vitamin C, as well as processed minerals and is considered as an essential health supplement51. Currently, four trials are registered which are investigating the preventive role of Chyawanprash in high risk healthcare workers/containment zone population as well as the community (Table III).

Yoga and naturopathy

Stress is known to suppress the immune system and is believed to be the harbinger of many diseases including respiratory infections52,53. Evidence supports the role of meditation in regulating the stress response and impacting virus-specific immune response54,55. Further, Pranayama has been shown to have a positive impact on lung function56. Currently, three yoga trials are registered, of which two randomized, parallel-group trials focus on the role of Pranayama and meditation in the prevention as well as treatment of COVID-19. In addition, in one trial, yoga is being tried in combination with naturopathy and Ayurvedic agents (CTRI/2020/05/025320).

Unani

The Unani system of medicine, originally from Greece, has been influenced by Ayurveda, Siddha and Chinese systems of medicine. Even though an ancient system, Unani medicine also recommends isolation and quarantine during an epidemic. In addition, it also recommends (i) cleanliness, (ii) health boosting and immune-modulation, and (iii) use of drugs57. Two trials investigating the prophylactic role of Unani medicine: one is on 4000 participants and the other on 40,000 participants, have been registered in population at risk of contracting COVID-19 (Table III).

Siddha

The Siddha system, one of the six accepted branches of Indian systems of medicine, is particularly popular in southern India. Although it is similar to Ayurveda in certain aspects, these are two distinct streams of medicine58. There are three Siddha trials registered investigating the role of Kabasura Kudineer, a Siddha formulation alone and in combination as a preventive agent in the management of asymptomatic COVID-19 patients (Table III).

Homeopathy

Homeopathy focuses on patient characteristics rather than disease per se59. There has been a call to utilize the benefits of homeopathy as a therapeutic system suitable to cope with this pandemic60,61. Several homeopathic agents have been recommended by the Ministry of AYUSH, Government of India, for the prevention of COVID-19. Of the 14 homeopathic trials registered in the CTRI, most (n=11) are of Arsenicum album 30 or Bryonia alba (Table III).

Miscellaneous trials

Thirteen trials have been categorized as miscellaneous trials as these explore a range of interventions such as nutraceuticals, process-of-care changes (n=9) and critical care-related trials and include management of non-COVID-19 patients in the pandemic (Table I). Some of these trials evaluate methods to minimize infection risks, whereas others compare different types of video laryngoscopes for ease of intubation while wearing personal protective equipment (Table IV). Some of the other registered trials in this category include efficacy of nutraceuticals, feasibility of developing a novel artificial intelligence algorithm to screen COVID-19, telemedicine and ventilatory management training to ramp up capacity.

Observational studies

Apart from the clinical trials, the CTRI has registered observational studies on COVID-19 as well. Due to the imposition of lockdown and the imperative need for social distancing, observational studies have been undertaken to assess the impact of COVID-19 on mental health, clinical practice in general and in particular for oncology patients. Findings and observations from these studies would likely help develop better guidelines for the care of the most vulnerable in these pandemic times.

Concluding remarks

Notwithstanding the deadly virulence of the SARS-CoV-2 and the enforcement of widespread physical restrictions, medical researchers in India have risen to the dual challenge of caring for the sick and testing potential therapeutic options. This article culls the data of 122 COVID-19-related trials from the data of over 27,000 trials registered in the CTRI and presents a concise and comprehensive overview of the pharmacological and clinical aspects of the registered trials. This also provides a comprehensive insight into the COVID-19 clinical research underway in the country through CTRI database. This would encourage researchers to critically review CTRI data, identify gaps particularly methodological and design aspects of research and further decide on acceptability of the results. We hope that this information would help researchers to not only understand the clinical research scenario, but also encourage healthy debate, train researchers to avoid obvious errors/oversights, steer clear of repetitive research and indirectly promote the quality of research in the country.

Acknowledgment:

The CTRI was set up with financial support from the ICMR, Ministry of Health and Family Welfare; Department of Science and Technology, Government of India; and World Health Organization, India Office, New Delhi, India. The CTRI website is hosted by the National Informatics Centre Services Inc., New Delhi, India. Authors acknowledge the support provided by the following: Servshri Anoop Upadhyay, Harish Kumar, and Din Bandhu, and Ms Noori Dua and Ms Deepty Rathi in the initial screening of the trials and typographical work.

Footnotes

Financial support & sponsorship: None.

Conflicts of Interest: None.

References

  • 1.Worldometers. COVID-19 coronavirus pandemic. [accessed on October 6, 2020]. Available from: https://www.worldometers.info/coronavirus/
  • 2.COVID-19 treatment guidelines. [accessed on June 11, 2020]. Available from: https://covid19treatmentguidelines.nih.gov/introduction/
  • 3.Clinical Trials Registry. India. [accessed on June 11, 2020]. Available from: http://www.ctri.nic.in/Clinicaltrials/login.php .
  • 4.World Health Organization. International Clinical Trials Registry Platform (ICTRP) [accessed on June 11, 2020]. Available from: https://www.who.int/ictrp/en .
  • 5.World Health Organization. “Solidarity” clinical trial for COVID-19 treatments. [accessed on June 11, 2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/globalresearch-on-novel-coronavirus-2019-ncov/solidarity-clinicaltrial-for-covid-19-treatments .
  • 6.Jordan PC, Stevens SK, Deval J. Nucleosides for the treatment of respiratory RNA virus infections. Antivir Chem Chemother. 2018;26:1–19. doi: 10.1177/2040206618764483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Pastick KA, Okafor EC, Wang F, Lofgren SM, Skipper CP, Nicol MR, et al. Hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19) Open Forum Infect Dis. 2020;7:ofaa130. doi: 10.1093/ofid/ofaa130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56:105949. doi: 10.1016/j.ijantimicag.2020.105949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Advisory on the use of hydroxychloroquine as prophylaxis for SARS-CoV-2 infection. 2020. [accessed on June 11, 2020]. Available from: https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf .
  • 10.Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014;2014:357027. doi: 10.1155/2014/357027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Sisk JM, Frieman MB, Machamer CE. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J Gen Virol. 2018;99:619–30. doi: 10.1099/jgv.0.001047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Cherian SS, Agrawal M, Basu A, Abraham P, Gangakhedkar RR, Bhargava B. Perspectives for repurposing drugs for the coronavirus disease 2019. Indian J Med Res. 2020;151:160–71. doi: 10.4103/ijmr.IJMR_585_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Singh V. Clinical outcome of a novel anti-CD6 biologic itolizumab in patients of psoriasis with comorbid conditions. Dermatol Res Pract. 2016;2016:1316326. doi: 10.1155/2016/1316326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Krupashankar DS, Dogra S, Kura M, Saraswat A, Budamakuntla L, Sumathy TK, et al. Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study. J Am Acad Dermatol. 2014;71:484–92. doi: 10.1016/j.jaad.2014.01.897. [DOI] [PubMed] [Google Scholar]
  • 15.Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55:105954. doi: 10.1016/j.ijantimicag.2020.105954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Chahar M, Rawat KD, Reddy PVJ, Gupta UD, Natarajan M, Chauhan DS, et al. Potential of adjunctive Mycobacterium w (MIP) immunotherapy in reducing the duration of standard chemotherapy against tuberculosis. Indian J Tuberc. 2018;65:335–44. doi: 10.1016/j.ijtb.2018.08.004. [DOI] [PubMed] [Google Scholar]
  • 17.Sehgal IS, Bhalla A, Puri GD, Yaddanapudi LN, Singh M, Malhotra P, et al. Safety of an immunomodulator Mycobacterium w in COVID-19. Lung India. 2020;37:279–1. doi: 10.4103/lungindia.lungindia_242_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Zhang R, Wang X, Ni L, Di X, Ma B, Niu S, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. doi: 10.1016/j.lfs.2020.117583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Moradkhani F, Moloudizargari M, Fallah M, Asghari N, Heidari Khoei H, et al. Immunoregulatory role of melatonin in cancer. J Cell Physiol. 2020;235:745–57. doi: 10.1002/jcp.29036. [DOI] [PubMed] [Google Scholar]
  • 20.Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. doi: 10.1016/j.antiviral.2020.104787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Xu J, Shi PY, Li H, Zhou J. Broad spectrum antiviral agent niclosamide and its therapeutic potential. ACS Infect Dis. 2020;6:909–15. doi: 10.1021/acsinfecdis.0c00052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Guthappa R. Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS-CoV-2 protease and its comparison with hydroxychloroquine. ChemRxiv. 2020 doi: 10.26434/chemrxiv.12161493.v1. [Google Scholar]
  • 23.Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.e8. doi: 10.1016/j.cell.2020.02.052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens Res. 2020;43:648–54. doi: 10.1038/s41440-020-0455-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Mittra I, Samant U, Sharma S, Raghuram GV, Saha T, Tidke P, et al. Cell-free chromatin from dying cancer cells integrate into genomes of bystander healthy cells to induce DNA damage and inflammation. Cell Death Discov. 2017;3:17015. doi: 10.1038/cddiscovery.2017.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Mittra I, Pal K, Pancholi N, Tidke P, Siddiqui S, Rane B, et al. Cell-free chromatin particles released from dying host cells are global instigators of endotoxin sepsis in mice. PLoS One. 2020;15:e0229017. doi: 10.1371/journal.pone.0229017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Ferruzzi MG, Failla ML, Schwartz SJ. Sodium copper chlorophyllin: in vitro digestive stability and accumulation by Caco-2 human intestinal cells. J Agric Food Chem. 2002;50:2173–9. doi: 10.1021/jf010869g. [DOI] [PubMed] [Google Scholar]
  • 28.Xi H, Kurtoglu M, Lampidis TJ. The wonders of 2-deoxy-D-glucose. IUBMB Life. 2014;66:110–21. doi: 10.1002/iub.1251. [DOI] [PubMed] [Google Scholar]
  • 29.Balkrishna A, Thakur P, Singh S, Dev S, Jain V, Varshney A, et al. Glucose antimetabolite 2-Deoxy- D-Glucose and its derivative as promising candidates for tackling COVID-19: Insights derived from in silico docking and molecular simulations. Authorea. 2020 doi: 10.22541/au.158567174.40895611. [Google Scholar]
  • 30.Balkrishna A, Pokhrel S, Singh J, Varshney A. Withanone from Withania Somnifera may inhibit novel coronavirus (COVID-19) entry by disrupting interactions between viral s-protein receptor binding domain and host ACE2 receptor. 2020 doi: 10.21203/rs.3.rs-17806/v1. [Google Scholar]
  • 31.Meena MK, Singh N, Meena R, Patni V. Quantitative determination of gallic acid from methanolic extract of Cocculus hirsutus using HTPLC. Int J Pharm Bio Arch. 2016;7:6–10. [Google Scholar]
  • 32.Khader M, Eckl PM. Thymoquinone: an emerging natural drug with a wide range of medical applications. Iran J Basic Med Sci. 2014;17:950–7. [PMC free article] [PubMed] [Google Scholar]
  • 33.Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, et al. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016;14:152–7. doi: 10.2450/2015.0131-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.World Health Organization. WHO Blood Regulators Network (BRN): Position paper on collection and use of convalescent plasma or serum as an element in Filovirus outbreak response. [accessed on June 11, 2020]. Available from: https://www.who.int/bloodproducts/brn/BRN_PositionPaperConvPlasmaFiloviruses_FINALWEB14August2014.pdf?ua=1 .
  • 35.Rajendran K, Krishnasamy N, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: Systematic review. J Med Virol. 2020 doi: 10.1002/jmv.25961. 10.1002/jmv.25961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Yang L, Tian D, Liu W. Strategies for vaccine development of COVID-19. Sheng Wu Gong Cheng Xue Bao. 2020;36:593–604. doi: 10.13345/j.cjb.200094. [DOI] [PubMed] [Google Scholar]
  • 37.Tanner R, Villarreal-Ramos B, Vordermeier HM, McShane H. The humoral immune response to BCG vaccination. Front Immunol. 2019;10:1317. doi: 10.3389/fimmu.2019.01317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Neelakantan V. Tuberculosis control in postcolonial South India and beyond: Fractured sovereignties in international health, 1948-1960. Wellcome Open Res. 2017;2:4. doi: 10.12688/wellcomeopenres.10544.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Miller A, Reandelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu GH. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv. 2020 doi: 10.1101/2020.03.24.20042937. [Google Scholar]
  • 40.Advisory from Ministry of AYUSH for meeting the challenge arising out of spread of coronavirus (COVID-19) in India. [accessed on June 11, 2020]. Available from: https://www.ayush.gov.in/docs/125.pdf .
  • 41.Mishra L, Singh BB, Dagenais S. Ayurveda: a historical perspective and principles of the traditional healthcare system in India. Altern Ther Health Med. 2001;7:36–42. [PubMed] [Google Scholar]
  • 42.Saha S, Ghosh S. Tinospora cordifolia: One plant, many roles. Anc Sci Life. 2012;31:151–9. doi: 10.4103/0257-7941.107344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi). validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res. 2010;1:112–21. doi: 10.4103/0974-7788.64405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): A review. Altern Med Rev. 2000;5:334–46. [PubMed] [Google Scholar]
  • 45.Ganguly B, Umapathi V, Rastogi SK. Nitric oxide induced by Indian ginseng root extract inhibits infectious Bursal Disease virus in chicken embryo fibroblasts in vitro. J Anim Sci Technol. 2018;60:2. doi: 10.1186/s40781-017-0156-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864. doi: 10.1155/2014/186864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.AYUSH-64. An ayurvedic antimalarial drug. [accessed on June 11, 2020]. Available from: http://www.ccras.nic.in/sites/default/files/viewpdf/IEC_Communication/Ayush%2064.pdf .
  • 48.Das D, Agarwal SK, Chandola HM. Protective effect of Yashtimadhu (Glycyrrhiza glabra) against side effects of radiation/chemotherapy in head and neck malignancies. Ayu. 2011;32:196–9. doi: 10.4103/0974-8520.92579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Maurya DK. Evaluation of Yashtimadhu (Glycyrrhiza glabra) active phytochemicals against novel coronavirus (SARS-CoV-2) Research Square. 2020 doi.org/10.21203/rs.3.rs-26480/v1. [Google Scholar]
  • 50.Gundeti MS, Bhurke LW, Mundada PS, Murudkar S, Surve A, Sharma R, et al. AYUSH 64, a polyherbal Ayurvedic formulation in Influenza like Illness: Results of a pilot study. J Ayurveda Integr Med. 2020 doi: 10.1016/j.jaim.2020.05.010. doi:10.1016/j.jaim.2020.05.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Sharma R, Martins N, Kuca K, Chaudhary A, Kabra A, Rao MM, et al. Chyawanprash: A traditional Indian bioactive health supplement. Biomolecules. 2019;9:161. doi: 10.3390/biom9050161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Salleh MR. Life event, stress and illness. Malays J Med Sci. 2008;15:9–18. [PMC free article] [PubMed] [Google Scholar]
  • 53.Maxwell L, Barrett B, Chase J, Brown R, Ewers T. Self-reported mental health predicts acute respiratory infection. WMJ. 2015;114:100–4. [PMC free article] [PubMed] [Google Scholar]
  • 54.Househam AM, Peterson CT, Mills PJ, Chopra D. The effects of stress and meditation on the immune system, human microbiota, and epigenetics. Adv Mind Body Med. 2017;31:10–25. [PubMed] [Google Scholar]
  • 55.Morgan N, Irwin MR, Chung M, Wang C. The effects of mind-body therapies on the immune system: Meta-analysis. PLoS One. 2014;9:e100903. doi: 10.1371/journal.pone.0100903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Budhi RB, Payghan S, Deepeshwar S. Changes in lung function measures following Bhastrika Pranayama (Bellows Breath) and running in healthy individuals. Int J Yoga. 2019;12:233–9. doi: 10.4103/ijoy.IJOY_43_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Nikhat S, Fazil M. Overview of Covid-19; its prevention and management in the light of Unani medicine. Sci Total Environ. 2020;728:138859. doi: 10.1016/j.scitotenv.2020.138859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Muthiah K, Ganesan K, Ponnaiah M, Parameswaran S. Concepts of body constitution in traditional Siddha texts: A literature review. J Ayurveda Integr Med. 2019;10:131–4. doi: 10.1016/j.jaim.2019.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Poitevin B. Integrating homoeopathy in health systems. Bull World Health Organ. 1999;77:160–6. [PMC free article] [PubMed] [Google Scholar]
  • 60.Kalliantas D, Kallianta M, Karagianni CS. Homeopathy combat against coronavirus disease (Covid-19) Z Gesundh Wiss. 2020:1–4. doi: 10.1007/s10389-020-01305-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Ministry of AYUSH, Government of India. Homeopathy for prevention of coronavirus infections. [accessed on June 11, 2020]. Available from: https://pib.gov.in/PressReleasePage.aspx?PRID=1600895 .

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