Table 2.
Summary of on-going parallel randomized controlled trials (RCTs) studying the efficacy and safety of herbal medicine treatment in patients with COVID-19.
| Trial Identifier | Sample Size Disease Stage No. of Trial Center |
Intervention (Regimen) | Control (Regimen) | Primary Outcome Measures | Secondary Outcome Measures | Registration Date Estimate Trial Duration |
|---|---|---|---|---|---|---|
| NCT 04251871 |
150 n.r. Single |
(A) HM (TCM granules, 2 times a day, for 14 days, n = n.r.), plus B | (B) WM (Alpha interferon (inhalation), and Lopinavir/ Ritonavir (oral) for 2 times a day, n = n.r.) | (1) Time to complete remission of symptoms (2) Symptoms’ change (fever and cough) |
The incidence of dyspnea with low oxygen saturation level and high respiratory rate/Number of subjects who develop complications/Time to virus shedding/Time to improvement of abnormalities in chest imaging/Improvement of TCM syndrome score | 5 February 2020 22 January 2020 to 22 January 2021 |
| ChiCTR 2000029418 |
32 severe Single |
(A) HM (n.r., n = 28), plus B | (B) WM (n.r., n = 14) | Percentage of patients progress to critically ill | Oxygenation index/Procalcitonin level/Percentage of antibiotic use | 30 January 2020 3 February to 31 August 2020 |
| ChiCTR 2000029434 |
240 n.r. Multiple (7) |
(A) HM (Lianhua Qingwen capsules/granules, 4 capsules or 1 bag for 3 times daily, n = 120), plus B | (B) WM (n.r., n = 120) | Clinical symptoms recovery rate and recovery time (fever, fatigue, cough) | Time and rate to negativity in RT-PCR nucleic acid test/Proportion of aggravation during treatment/Rate of improvement of abnormalities in chest CT/Single symptom disappearance rate and main symptom disappearance time/Disease recovery rate/Routine blood test/Biochemical indicators | 1 February 2020 1 February to 1 December 2020 |
| ChiCTR 2000029438 |
100 severe or critical Single |
(A) HM (n.r., n = 50), plus B | (B) WM (n.r., n = 50) | (1) CURB-65 score (2) PSI score (3) Mechanical ventilation time (4) Length of stay in hospital |
Time to reduce fever /Pulmonary function/Mortality and recovery rate/Rate of multiple organ dysfunction/Time to negativity in RT-PCR nucleic acid test/Inflammation index/Incidence of AEs | 1 February 2020 1 February 2020 to 1 December 2021 |
| ChiCTR 2000029439 |
120 moderate Multiple (2) |
(A) HM (n.r., n = 60), plus B | (B) WM (n.r., n = 60) | (1) Time to reduce fever (2) Time to negativity in RT-PCR nucleic acid test |
Pulmonary function/Rate of patients’ progress to severe stage/Inflammation index/Disappearance time of gastrointestinal symptoms/TCM syndrome score/Incidence of AEs | 1 February 2020 1 February to 31 December 2020 |
| ChiCTR 2000029461 |
100 moderate Multiple (2) |
(A) HM (n.r., n = 50), plus B | (B) WM (n.r., n = 50) | (1) Pulmonary function (2) Time to reduce fever (3) Time to negativity in RT-PCR nucleic acid test |
Disappearance time of cough/Incidence of AEs/St George’s respiratory questionnaire/Modified Barthel Index/6-min walk test | 2 February 2020 3 February to 31 December 2021 |
| ChiCTR 2000029518 |
140 moderate or severe Single |
(A) HM (n.r., n = 70), plus B | (B) WM (n.r., n = 70) | (1) Recovery time (2) Ratio and time for the moderate patients to progress to severe (3) Ratio and time for severe patients to progress to critical or death |
Improvement of TCM syndrome score/Relief of clinical symptoms (fever, fatigue, gastrointestinal discomfort, etc.) and duration/Lung HRCT score improvement/Average length of hospital stay/Adverse event rate/Quality of life (SF 36) | 3 February 2020 4 February to 30 April 2020 |
| ChiCTR 2000029549 |
400 mild or moderate Single |
(A) HM (n.r., n = 200), plus B | (B) WM (n.r., n = 200) | (1) Rate of patient’s progress to severe stage (2) Oxygenation index (3) Time to negativity in RT-PCR nucleic acid test (4) Improvement of abnormalities in chest CT |
n.r. | 4 February 2020 3 February to 1 May 2020 |
| ChiCTR 2000029747 |
200 n.r. Multiple (4) |
(A) HM (n.r., n = 100) | (B) WM (n.r., n = 100) | (1) Improvement of abnormalities in chest CT (2) Routine blood test (3) Liver and renal function (4) Improvement of TCM syndrome score |
n.r. | 11 February 2020 1 February 2020 to 10 February 2021 |
| ChiCTR 2000029755 |
120 mild or moderate Single |
(A) HM (Jinyebaidu granule, 1‒2 packets, 3 times daily, n = 60), plus B | (B) WM (n.r., n = 60) | Effective index | Safety index | 12 February 2020 12 February to 30 May 2020 |
| ChiCTR 2000029763 |
408 n.r. Single |
(A) HM (n.r., n = 204), plus B | (B) WM (n.r., n = 204) | Rate of patients progress to severe or critical illness | Rate of isolation discharge/Improvement of TCM syndrome score/Body temperature/Blood routine test/Blood biochemical test/Improvement of abnormalities in chest imaging/Psychological outcomes | 12 February 2020 12 February to 31 May 2020 |
| ChiCTR 2000029769 |
40 severe Single |
(A) HM (Babaodan, 6 capsules, 2 times daily, n = 20), plus B | (B) WM (n.r., n = 20) | (1) 28-day survival rate (2) Inflammatory factor levels |
n.r. | 13 February 2020 15 February to 30 April 2020 |
| ChiCTR 2000029777 |
160 n.r. Single |
(A) HM (Truncation and Torsion Formula, n = 80), plus B | (B) WM (n.r., n = 80) | (1) Responses after 14 days (recovery, improvement, turning critical, death) (2) Improvement of abnormalities in chest CT |
Vital signs/Oxygenation index/Routine blood test/Inflammatory biomarkers/Major organ function/Coagulation index/APACHE II | 13 February 2020 1 February to 30 June 2020 |
| ChiCTR 2000029788 |
60 mild Single |
(A) HM (n.r., n = 30), plus B | (B) WM (n.r., n = 30) | (1) Time to reduce fever (2) Time to negativity in RT-PCR nucleic acid test (3) Blood gas analysis (4) Improvement of TCM syndrome score |
n.r. | 13 February 2020 31 March to 30 December 2020 |
| ChiCTR 2000029790 |
120 n.r. Single |
(A) HM (n.r., n = 60), plus B | (B) WM (n.r., n = 60) | Improvement of TCM syndrome score | Rate of patients’ progress to severe or critical illness/Time to negativity in RT-PCR nucleic acid test/Time to reduce fever/Length of stay in hospital | 13 February 2020 17 February to 31 October 2020 |
| ChiCTR 2000029813 |
72 mild or moderate Single |
(A) HM (Tanreqing, 3 capsules for 3 times daily, n = 36), plus B | (B) WM (n.r., n = 36) | (1) Time to negativity in RT-PCR nucleic acid test (2) Time to reduce fever |
Arterial oxygen saturation/Rate of patients’ progress to severe or critical illness/Inflammation index (CRP)/The disappearance rate and time of cough symptoms/Clinical recovery time | 14 February 2020 14 February to 14 August 2020 |
| ChiCTR 2000029822 |
110 n.r. n.r. |
(A) HM (Jinyinhua Tang, n = 70) | (B) Placebo (n.r., n = 40) | Effective rate | Time to reduce fever/Pulmonary symptoms and measure/Length of stay in hospital | 14 February 2020 7 February to 30 April 2020 |
| ChiCTR 2000029869 |
300 n.r. Multiple (3) |
(A) HM (Baidu Jieduan formula, n = 150), plus B | (B) WM (n.r., n = 150) | (1) Responses after 14 days (recovery, improvement, turning critical, death) (2) Improvement of abnormalities in chest CT |
Pneumonia symptoms/Oxygenation index/Routine blood test/Major organ function/Coagulation index/Inflammatory biomarkers | 15 February 2020 1 February to 30 June 2020 |
| ChiCTR 2000029941 |
200 mild, moderate, or severe Multiple (5) |
(A) HM (Zhongyao Fufang granules, n = 100), plus B | (B) WM (n.r., n = 100) | Incidence of aggravation events | Total duration of disease/Length of stay in hospital/Time to total recovery/Time to negativity in RT-PCR nucleic acid test/Time from treatment to the beginning of antipyretic/Time from treatment to complete antipyretic/Improvement of abnormalities in chest imaging/Incidence of AEs | 17 February 2020 1 March to 1 June 2020 |
| ChiCTR 2000029947 |
200 n.r. Multiple (5) |
(A) HM (Zhongyao Fufang granules, n = 100), plus B | (B) WM (n.r., n = 100) | Lung function | Total duration of disease/Time to total recovery/Incidence of AEs/Incidence of sequelae/Quality of life (SF 36)/Mental health scale | 17 February 2020 1 March to 1 June 2020 |
| ChiCTR 2000029960 |
100 n.r. Single |
(A) HM (n.r., n = 70), plus B | (B) WM (n.r., n = 30) | Improvement of TCM syndrome score | n.r. | 17 February 2020 21 February to 31 May 2020 |
| ChiCTR 2000030034 |
132 n.r. Multiple (7) |
(A) HM (n.r., n = 88), plus B | (B) WM (n.r., n = 44) | (1) Body temperature (2) Improvement of TCM syndrome score (3) Murray Score for Acute Lung Injury (4) Time to negativity in RT‒PCR nucleic acid test (5) MuLBSTA score |
n.r. | 21 February 2020 1 February to 30 June 2020 |
| ChiCTR 2000030166 |
20 n.r. Single |
(A) HM (Qingwen Baidu Yin granules, n = 10), plus B | (B) WM (Lopinavir‒ritonavir tablets + recombinant human interferon alpha 2b injection, n = 10) | (1) Improvement of abnormalities in chest CT (2) Nucleic acid detection of throat secretion |
Body temperature/3CL Mpro of Coronavirus/Routine blood test/ Routine urine test/Liver function test/Renal function test/Routine stool test | 24 February 2020 25 February to 14 May 2020 |
| ChiCTR 2000030188 |
120 n.r. Single |
(A) HM (n.r., n = 80), plus B | (B) WM (n.r., n = 40) | (1) Improvement of TCM syndrome score (2) Time to negativity in RT-PCR nucleic acid test (3) Cure/mortality rate |
Major symptom remission time/Blood gas analysis/Indicators of inflammation (CRP, ESR)/Improvement of abnormalities in chest CT | 24 February 2020 15 February to 30 March 2020 |
| ChiCTR 2000030288 |
104 mild or moderate Single |
(A) HM (n.r., n = 102), plus B | (B) WM (n.r., n = 102) | Time to negativity in RT-PCR nucleic acid test | The 7-point scale/Rate of patients’ progress to severe or critical illness/Routine blood test/Blood biochemical test | 27 February 2020 27 February to 31 December 2020 |
| ChiCTR 2000030469 |
96 moderate or severe Single |
(A) HM (Liu Shen Wan, n = 48), plus B | (B) WM (n.r., n = 48) | (1) Time to reduce fever (2) Effective rate of TCM symptoms |
Body temperature/Improvement of abnormalities in chest CT/Time to negativity in RT-PCR nucleic acid test/Oxygen saturation/Length of stay in hospital/Rate of patients’ progress to severe or critical illness/Improvement of TCM syndrome score/Routine blood test | 2 March 2020 27 February to 27 May 2020 |
| ChiCTR 2000030479 |
100 moderate Multiple (3) |
(A) HM (Yiqi Huashi Jiedu Fang, n = 50), plus B | (B) WM (n.r., n = 50) | (1) Time to reduce fever (2) Time to negativity in RT-PCR nucleic acid test |
Improvement of TCM syndrome score/Changes in inflammation indicators/Changes in SpO2, oxygen saturation, lymphocyte count/Time to clinical recovery/Rate of patients progress to severe or critical illness | 3 March 2020 26 February 2020 to 25 February 2021 |
| ChiCTR 2000030522 |
100 mild or moderateMultiple (3) | (A) HM (Ma Xing Shi Gan Tang, n = 50), plus B | (B) WM (n.r., n = 50), plus Placebo | Time to clinical recovery | Time to reduce fever/Time to negativity in RT-PCR nucleic acid test/Rate of patients’ progress to severe or critical illness/Laboratory tests (white blood cell and lymphocyte count, erythrocyte sedimentation rate, CRP/ Improvement of abnormalities in chest CT/Improvement of TCM syndrome score | 5 March 2020 9 March to 9 September 2020 |
| ChiCTR 2000030759 |
60 n.r. Multiple (3) |
(A) HM (n.r., n = 56), plus B | (B) WM (n.r., n = 14) | (1) Time to negativity in RT-PCR nucleic acid test (2) Incidence of aggravation events (3) Time to reduce fever (4) Improvement of abnormalities in chest CT (5) Major symptom remission rate |
Blood count/CRP/Blood gas analysis/Routine urine test/Blood lipid, Blood glucose, Coagulation function test/Liver function test, renal function/Myocardial enzymes/Serum procalcitonin, T-lymphocyte subsets, Interleukin | 13 March 2020 15 February to 17 May 2020 |
| ChiCTR 2000030936 |
2840 n.r. Multiple (71) |
(A) HM (Xinguan No. 2/Xinguan No. 3, n = 2130), plus B | (B) WM (n.r., n = 710) | (1) Time to reduce fever (2) Disappearance rate of TCM symptoms |
n.r. | 18 March 2020 10 March to 10 May 2020 |
| ChiCTR 2000030937 |
144 n.r. Multiple (6) |
(A) HM (Gu Shen Ding Chuan Wan, n = 72), plus B | (B) WM (n.r., n = 72) | (1) Changes in TCM syndrome (2) Changes of fatigue assessment scale |
n.r. | 18 March 2020 19 March to 30 August 2020 |
| ChiCTR 2000030988 |
204 mild, moderate, or severe Single |
(A) HM (Hua Shi Bai Du granules, n = 102), plus B | (B) WM (n.r., n = 102) | Improvement of abnormalities in chest CT | Length of stay in hospital/Incidence of AEs | 20 March 2020 20 March to 31 May 2020 |
AEs: adverse events; APACHE II, acute physiology and chronic health evaluation II; CRP, C-reactive protein; CURB-65, confusion, urea, respiratory rate, blood pressure, and 65 years of age or older; ESR, erythrocyte sedimentation rate; HM, herbal medicine; HRCT, high-resolution computed tomography; MuLBSTA, multi-lobular infiltration, lymphopenia, bacterial co-infection, smoking history, hypertension and age; n.r., not reported; PSI, pneumonia severity index; RT-PCR, reverse transcription polymerase chain reaction; TCM, traditional Chinese medicine; WM, Western medicine; 3CL Mpro, 3C-like proteinase.