Table 3.
Shows the Clinical Trials Registered on ClinicalTrials.gov To October 20, 2020, Utilizing Prospective Therapies for the Treatment of COVID-19
| Therapy Modality | Study Identifier and Citation (Superscript) | Treatment Protocol | Study Phase; Estimated Enrolment (n) | Primary Outcome Measure(s) | Recruitment Status |
|---|---|---|---|---|---|
| Recombinant ACE2 receptors | NCT04375046149 | Experimental: Experimental: rbACE2 group 0.4 mg/kg IV BID for 7 days (unblinded) + standard of care Intervention: drug: recombinant bacterial ACE2 receptors—like enzyme of B38-CAP (rbACE2) No intervention: no Intervention: control group Standard of care; no placebo |
Phase I n=24 |
Time course of body temperature (fever) (time frame: 14 days) Compare the time course of body temperature (fever) between two groups over time. Viral load over time (time frame: 14 days) Compare viral load between two groups over time. |
Not yet recruiting |
| NCT04382950150 | Experimental: Experimental: rbACE2 group plus aerosolized isotretinoin rbACE2 0.4 mg/kg IV BID for 7 days (unblinded) plus aerosolized 13 cis retinoic acid in gradual in 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled 13 cis retinoic acid therapy for 14 days Intervention: combination product: recombinant bacterial ACE2 receptors—like enzyme of B38-CAP (rbACE2) plus aerosolized 13 cis retinoic acid No intervention: no Intervention: control group Standard of care; no placebo |
Phase I n=24 |
Viral load over time (time frame: 14 days) Compare viral load between two groups over time. P/F ratio over time (time frame: 14 days) PaO2/FiO2 ratio Sequential organ failure assessment score (SOFA score) over time (time frame: 14 days) SOFA, including assessment of respiratory, blood, liver, circulatory, nerve, kidney, from 0 to 4 scores in each systems, the higher scores mean a worse outcome. Pulmonary severity index (PSI) (time frame: 14 days) Image examination of chest over time (time frame: 14 days) Based on radiologist’s assessment of inflammatory exudative disease, category as follows: significant improvement, partial improvement, no improvement, increase of partial exudation, significant increase in exudation, unable to judge. Proportion of subjects who progressed to critical illness or death (time frame: at 14 days) Time from first dose to conversion to normal or mild pneumonia (time frame: 14 days) T-lymphocyte counts over time (time frame: 14 days) C-reactive protein levels over time (time frame: 14 days) Angiotensin II (Ang II) changes over time (time frame: 14 days) Angiotensin 1–7 (Ang 1–7) changes over time (time frame: 14 days) Angiotensin 1–5 (Ang 1–5) changes over time (time frame: 14 days) Renin changes over time (time frame: 14 days) Aldosterone changes over time (time frame: 14 days) Angiotensin-converting enzyme (ACE) changes over time (time frame: 14 days) Interleukin 6 (IL-6) changes over time (time frame: 14 days) Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time (time frame: 14 days) Plasminogen activator inhibitor type-1 (PAI-1) changes over time (time frame: 14 days) Von Willebrand factor (VWF) changes over time (time frame: 14 days) Tumor necrosis factor-α (TNFα) changes over time (time frame: 14 days) Soluble receptor for advanced glycation end products (sRAGE) changes over time (time frame: 14 days) Surfactant protein-D (SP-D) changes over time (time frame: 14 days) Frequency of adverse events and severe adverse events(time frame: 14 days) |
Not yet recruiting | |
| Exosomes | NCT04491240151 | Procedure: EXO 1 inhalation Twice a day during 10 days inhalation of 3 mL special solution contained 0.5–2⨰10^10 of nanoparticles (exosomes) of the first type. Procedure: EXO 2 inhalation Twice a day during 10 days inhalation of 3 mL special solution contained 0.5–2⨰10^10 of nanoparticles (exosomes) of the second type. Procedure: placebo inhalation Twice a day during 10 days inhalation of 3 mL special solution free of nanoparticles (exosomes) |
Phase I PhaseII n=90 |
Number of participants with non-serious and serious adverse events during trial (time frame: 30 days after clinic discharge) Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial Number of participants with non-serious and serious adverse during inhalation procedure (time frame: after each inhalation during 10 days) Safety assessments such as adverse events during the inhalation procedures will be registered |
Enrolling by invitation |
| NCT04389385152 | Biological: COVID-19 specific T cell derived exosomes (CSTC-Exo) | Phase I n=60 |
Adverse reaction (AE) and severe AE (SAE) (time frame: 28 days) Safety assessment efficacy assessment (time frame: 28 days) Time to clinical recovery (TTCR) The rate of recovery without mechanical ventilator (time frame: 28 days) Efficacy assessment |
Not yet recruiting | |
| MSCs | NCT04384445153 | Zofin is an acellular, minimally manipulated product, derived from human amniotic fluid (HAF). This product contains over 300 growth factors, cytokines, and chemokines as well as other extracellular vesicles/nanoparticles derived from amniotic stem and epithelial cells. Biological: zofin Biological: zofin will be administered intravenously with 1 mL, containing 2–5⨰10^11 particles/mL in addition to the standard care. The zofin dose will be diluted in 100 mL of sterile saline at subject’s bedside. Participants in this group will receive standard of care plus zofin on day 0, day 4 and day 8. Intervention: Biological: zofin Other: placebo Other: placebo Placebo (saline) will be administered intravenously with 1 mL in addition to the standard care. The placebo dose will be diluted in 100 mL of sterile saline at subject’s bedside. Participants in this group will receive standard of care plus placebo (saline) on day 0, day 4 and day 8. |
Phase I Phase II n=20 |
Incidence of any infusion associated adverse events (time frame: 60 days) Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician Incidence of severe adverse events (time frame: 60 days) Safety will be defined by the incidence of severe adverse events as assessed by treating physician |
Recruiting |
| NCT04276987154 | Experimental: MSCs-derived exosomes treatment group Conventional treatment and aerosol inhalation of MSCs-derived exosomes treatment participants will receive conventional treatment and 5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 mL at days 1, 2, 3, 4, and 5). Intervention: Biological: MSCs-derived exosomes |
Phase I n=24 |
Adverse reaction (AE) and severe adverse reaction (SAE) (time frame: up to 28 days) Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE) Time to clinical improvement (TTIC) (time frame: up to 28 days) Efficiency evaluation within 28 days, including time to clinical improvement (TTIC) |
Completed | |
| NCT04457609155 | Drug: oseltamivir Current standardized treatment for COVID-19 Drug: azithromycin Current standardized treatment for COVID-19 Biological: umbilical cord MSCs Adjuvant therapy on top of current standardized treatment (oseltamivir+azithromycin) |
Phase I n=40 |
Clinical improvement: presence of dyspnea (time frame: 15 days) Assessing whether the patients still have dyspnea, one of cardinal symptoms of COVID-19, assessed from the respiratory rate Clinical improvement: presence of sputum (time frame: 15 days) Assessing whether the patients still have productive cough, one of cardinal symptoms of COVID-19, assessed from lung auscultation Clinical improvement: fever (time frame: 15 days) Assessing the presence of fever from measurement of body temperature checking, assessed on daily basis Clinical improvement: ventilation status (time frame: 15 days) Assessing whether the patients still require ventilation, one of cardinal symptoms of ARDS in COVID-19, assessed from patients’ ability during ventilation weaning phase Clinical improvement: blood pressure (time frame: 15 days) Assessing the patients’ blood pressure on daily basis Clinical improvement: heart rate (time frame: 15 days) Assessing the patients’ heart rate on daily basis Clinical improvement: respiratory rate (time frame: 15 days) Assessing the patients’ respiratory rate on daily basis Clinical improvement: oxygen saturation (time frame: 15 days) Assessing the patients’ oxygen saturation on daily basis |
Recruiting | |
| RAS blockers | NCT04331574156 | Observational model: Case-only time perspective: cross-sectional Patients with certified diagnosis of COVID-19 recruited in Italian hospitals |
Phase: not applicable n=2000 |
Numbers of COVID-19 patients enrolled that use ACE inhibitors and/or angiotensin receptor blockers (ARB) as antihypertensive agents (time frame: 3 months) Using anamnestic data collected from the health record of the hospital or of the general practitioner, we will count the number of COVID-19 patients enrolled that were treated with ACE Inhibitors or ARB. Numbers of COVID-19 patients enrolled with no symptoms, with moderate symptoms or with severe symptoms of pneumonia based on the WHO specification for ARDS that also used ACE inhibitors and/or angiotensin receptor blockers (ARB) as antihypertensive agents (time frame: 3 months) This study wants to observe whether the assumption of antihypertensive ACE inhibitors or ARB increases the severity of the clinical manifestation of COVID19 |
Recruiting |
| NCT04329195157 | Drug: 1: discontinuation of RAS blocker therapy discontinuation of RAS blocker therapy Drug: 2: continuation of RAS blocker therapy continuation of RAS blocker therapy |
Phase III n=554 |
Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first) (time frame: from day 0 to day 28 or hospital discharge) | Recruiting | |
| NCT04353596158 | Drug: ACE inhibitor, angiotensin receptor blocker In patients randomized to stopping/replacing ACEI or ARB, it may be necessary to switch to another drug without direct effect on the RAS system. In patients, randomized to continuation, it may be needed to stop ACEI or ARB (eg hypotension with beginning sepsis) irrespective of the study. |
Phase IV n=208 |
Combination of maximum sequential organ failure assessment (SOFA) score and death (time frame: 30 days) The minimal value of the SOFA score will be 0 and the maximal value 24 points. All-cause death is classified as the maximum score (24 points). In case of a subclinical disease progress without need for hospitalization, the SOFA score will be 0. Composite of admission to an ICU, the use of mechanical ventilation, or all-cause death (time frame: 30 days) |
Recruiting | |
| Traditional Chinese medicines | NCT04306497159 | Drug: TCM prescriptions TCM prescriptions 1: take decocted or granule, one dose a day; TCM prescriptions 2: take decocted or granule, one dose a day. |
Phase—no information n=340 |
The relief of main symptoms/disappearance rate of time (time frame: 9 days) Comparison of the time of relief/disappearance of three main symptoms of fever, cough and shortness of breath chest CT absorption (time frame: 9 days) with reference to the “pneumonia chest X-ray absorption evaluation scale” developed by Renyi Yin et al, the final absorption judgment will be used to evaluate the chest CT absorption of patients with pneumonia, which is divided into four levels according to the degree of absorption: complete absorption, majority absorption, partial absorption and no absorption. |
Completed |
| NCT04251871160 | Drug: conventional medicines (oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and TCMs granules Conventional medicines: oxygen therapy, antiviral therapy (alfa interferon via aerosol inhalation, and lopinavir/ritonavir, 400 mg/100 mg, p.o., bid) for 14 days. TCMs granules: 20 g, p.o., bid, for 14 days. Drug: conventional medicines (oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) Conventional medicines: oxygen therapy, antiviral therapy (alfa interferon via aerosol inhalation, and lopinavir/ritonavir, 400 mg/100 mg, p.o., bid) for 14 days. |
Not applicable n=150 |
The incidents of acute respiratory distress syndrome (ARDS) development (time frame: 14 days) The incidence rate of acute respiratory distress syndrome (ARDS) development |
Recruiting | |
| Antioxidants | NCT04363216161 | Drug: Ascor® ascorbic acid 2-h infusion daily (for 6 days), escalating dose (0.3 g/kg, 0.6 g/kg, 0.9 g/kg). Other name: vitamin C |
Phase II n=66 |
Clinical Improvement (time frame: 72) •Clinical improvement at 72-h of treatment, defined as a 50% reduction in the highest flow rate of oxygen during the 72-h period, a 50% reduction in the most frequent use of bronchodilators within a 12-h window within the 72-h period, or hospital discharge (whichever comes first). |
Not yet recruiting |
| NCT04323514162 | Dietary supplement: vitamin C 10 g of vitamin C IV in addition to conventional therapy. |
Not applicable n=500 |
In-hospital mortality (time frame: 72 h) Change of hospital mortality |
Recruiting | |
| NCT04519034163 | Audit 1 All vitamin D results performed since January 2020 (n= ~15,000) together with age, weight and height if available, ethnicity and other relevant laboratory markers (Ca, adjusted calcium, PTH, Mg, phosphate, liver and renal profile, COVID-19 screening, CRP, hematinics, FBC) Intervention: other: no intervention Audit 2 all COVID-19 screening results together with vitamin D, ethnicity, age, weight, height, length of stay in hospital including ICU (if applicable), type of illness, recovered or not, associated health conditions, CRP, ferritin, hematinics, vitamin A and E, procalcitonin, LDH, INR, fibrinogen, FBC, D-dimers, CK, troponin-T, cytokines, renal function and electrolytes from patients tested at GSTT NHS Trust. Intervention: other: no intervention |
Phase—not applicable n=27,000 |
Collecting vitamin D results in patients from the South-East London area together with age, sex, ethnicity and BMI and other relevant laboratory results. (time frame: January–June 2020) All vitamin D results performed by the Nutristasis Unit at St. Thomas’ since January 2020 (n= ~15,000) together with age, weight and height if available, ethnicity and other relevant laboratory markers (Ca, adjusted calcium, PTH, Mg, phosphate, liver and renal profile, COVID-19 screening, CRP, hematinics, FBC) if they were tested within two weeks of the sample being measured for vitamin D will be acquired. The results of this audit will provide us with a snap shot of vitamin D status in patients from the South-East London area by age, sex, ethnicity and BMI (weight in kg/height2). Correlation analysis will also be undertaken with other laboratory parameters. |
Not yet recruiting | |
| NCT04323228164 | Experimental: intervention—- the intervention groups will receive daily oral antioxidant supplement enriched in vitamins A, C, E, selenium and zinc. The composition of one capsule of the intervention-supplement includes: 1500 µg vitamin A (as β-carotene), 250 mg vitamin C, 90 mg vitamin E, 15 µg selenium, and 7.5 mg zinc. Intervention: dietary Supplement: oral supplement enriched in antioxidants Placebo comparator: placebo Placebo group will receive daily intervention in form of cellulose-containing gelatin capsules with the same color and shape. Intervention: dietary Supplement: cellulose-containing placebo capsules |
Phase II Phase III n=40 |
Change from baseline score of nutrition risk screening-2002 (NRS-2002) at end of the trial (time frame: up to 3 months) Changes in scores of the NRS-2002 for patients with COVID-19 at the end of the study, from 0 to 7 scores, with those scores <3 means no risk of malnutrition and ≥3 means malnutrition. Change from baseline serum ferritin level at end of the trial (time frame: up to 3 months) Change in serum ferritin at the end of the trial as ferritin is considered as a COVID-19 fatality predictor. Change from baseline serum IL-6 concentration at end of the trial (time frame: up to 3 months) Change in IL-6 at the end of the trial as it represents the cytokine storm and it is considered as a COVID-19 fatality predictor Change from baseline serum C-reactive protein concentration at end of the trial (time frame: up to 3 months) Change in C-reactive protein in the serum at the end of the trial which reflects the acute phase Change from baseline serum TNFα concentration at end of the trial (time frame: up to 3 months) Change in the TNF a in the serum at the end of study as it represents severity of the cytokine storm Change from baseline serum monocyte chemoattractant protein 1 (MCP-1) at end of the trial (time frame: up to 3 months) plasma MCP-1 represents severity of the cytokine storm |
Recruiting | |
| Dietary Supplement | NCT04382040165 | ArtemiC is a medical spray comprised of artemisinin (6 mg/mL), curcumin (20 mg/mL), frankincense (=Boswellia) (15 mg/mL) and vitamin C (60 mg/mL) in micellar formulation for spray administration. Drug: ArtemiC: Treatment will be sprayed orally twice a day for the first 2 days in the treatment period Drug: placebo: Treatment will be sprayed orally twice a day for the first 2 days in the treatment period |
Phase II n=50 |
Time to clinical improvement, defined as a national early warning score 2 (NEWS2) of ≤ 2 maintained for 24 h in comparison to routine treatment (time frame: 24 hours) patient will be assessed using a scoring table for changes in clinical signs Percentage of participants with definite or probable drug related adverse events (time frame: 14 days) adverse events caused by the study drug will be assessed |
Recruiting |
| NCT04347382166 | Experimental: Nigella sativa and honey group Drug: Nigella sativa seed Powder 80 mg/kg/day ground in a capsule up to a max of 14 days) Drug: natural honey 1 mg/kg/day orally up to a max of 14 days) along with standard medical care Interventions: Drug: honey; Drug: Nigella sativa/black cumin placebo comparator- standard medical Care: standard supportive medical care prescribed by treating physician, Lahore which includes standard symptomatic care along with use of antibacterial or antiviral (if advised by pulmonologist or infectious disease specialist) Intervention: Drug: placebos: |
Phase III n=313 |
Days required to get a positive COVID-19 PCR to negative (time frame: up to max 14 days) RT-PCR will be done on admission day (0 day) and then after every fourth day for 14 days or till the symptoms resolved and RT-PCR gets negative. RT-PCR will only be shown as positive or negative (as per limitation of Pakistan). HRCT/X-ray findings of disease progression (time frame: up to max 14 days] HRCT will be conducted at admission day (0-day) and a total of maximum four CT-scans will be conducted after every fourth day. The minimum and score at which we label COVID-19 positive will be 5 and 25 respectively using internationally standard nomenclature as described by Fleischner Society glossary and peer-reviewed literature on viral pneumonia. Severity of symptoms progression (time frame: up to max 14 days) Clinically disease progression will be evaluated depending upon the severity of symptoms being classified as mild, moderate and severe. Duration of hospital stay (time frame: up to max 14 days) Duration of hospital stay would be categorized as the number of days the patient stayed in the ward during treatment. The date of admission and date of discharge would give us total duration of stay. 30 day mortality (time frame: 30 days) 30 days mortality rate in each arm |
Completed | |
| NCT04323345167 | Dietary supplement: natural honey: natural honey supplement 1 g/kg/day divided into 2 to 3 doses for 14 days either orally or through nasogastric tube. Other: Standard Care: supportive measures and lopinavir/ritonavir tablets or arbidol or chloroquine phosphate or hydroxychloroquine or oseltamivir with or without azithromycin. |
Phase III n=1000 |
Rate of recovery from positive to negative swaps (time frame: 14 days) Percentage of patients turned from positive to negative swaps at day 14 Fever to normal temperature in days (time frame: 14 days) Number of days till no fever Resolution of lung inflammation in CT or X- ray(time frame: 30 days) Number of days till lungs recovery in chest X-ray or CT |
Recruiting | |
| NCT04342689168 | Drug: dietary supplement containing resistant starch: two tablespoons (~20 g) to be taken twice daily for 14 days (start with 2 tablespoons once daily for three days, followed by twice daily on days 4 through 14) (Other name: resistant starch) Dietary supplement: placebo starch: two tablespoons (~20 g) to be taken twice daily for 14 days (start with 2 tablespoons once daily for three days, followed by twice daily on days 4 through 14) (other name: nonresistant starch) |
Phase III n=1500 |
Rates of hospitalization for a COVID-19 related complication (time frame: One month from the start of treatment) Subject hospitalized while presenting symptoms of fever, shortness of breath, myalgia, cough, or hypoxia with an admission diagnosis of hypoxic respiratory failure, pneumonia, or viral pneumonia on review of electronic health record (EHR). Death prior to hospitalization thought to be secondary to COVID-19 will also be defined as an event. All hospital admissions will be reviewed and adjudicated by a site PI. |
Recruiting |