Table 1: Characteristics of included randomized trials investigating the efficacy and safety of SARS-Cov-2 virus.

 

Study

Location

Design

Age

(mean, years)

Follow-up (days)

Proportion of men participants

Dosing Information, number of participants randomized in each treatment group

Main primary endpoints

Sponsorship

Chen Jun, et al. [17]

China

Open-label, RCT

46.7-50.5

15

70%

400 mg Hydroxychloroquine (HCQ) orally for times daily for 5 days (n = 15);

Standard of care (bed rest, oxygen inhalation, antiviral drugs as lopinavir/ritonavir, and antibacterial drugs if necessary; n = 15)

Negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization.

 

NR

Li Ling, et al. [20]

China

Open-label, RCT

70

28

58.3%

4 to 13 ml/kg Convalescent plasma transfusion (n = 51);

Standard of care (antiviral, antibacterial medications, steroids, human immunoglobulin, Chinese herbal medicines; n = 51)

Time-to-clinical improvement within a 28-day period; clinical improvement was defined as patient discharge or a reduction of 2 points on a 6-point disease severity scalea.

 

CIFMS

Cao, et al. [24]

China

Open-label, RCT

58b

28

60.3%

400 mg and 100 mg of the oral combination Lopinavir/Ritonavir respectively twice a day for 14 days (n = 99);

Standard of care (supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and ECMO; n = 100)

Time-to-clinical improvement within a 28-day period, defined as time from randomization to either an improvement of two points on a seven-category ordinal scalea or discharge from the hospital, whichever came first.

 

Major Projects of national Science and Technology on NDCD

Wang, et al. [22]

China

RCT, double-blind

65b

28

59.1%

200 mg on day 1 and 100 mg on days 2 to 10 in single daily infusions of Remdesivir (n = 158); placebo (n = 79)

 

Time-to-clinical improvement within a 28-day period, defined as time from randomization to either an improvement of two points on a seven-category ordinal scalea or discharge from the hospital, whichever came first.

CAMSEP of Covid-19, NKRDPC, and BSTP

Borba Silva, et al. [23]

Brazil

RCT, phase IIb, double-blind

51.1

28

75.3%

600 mg Hydroxychloroquine (HCQ) or high-dose orally or via nasogastric tube (4 150 mg tablets twice daily for 10 days; total dose 12 g; n = 41);

450 mg HCQ or low-dose (3 150 mg tablets and 1 placebo tablet twice daily on day 0, 3 150 mg tablets and 1 placebo tablet once a day followed by 4 placebo tablets from day 1 to day 4, then 4 placebo tablets twice daily from day 5 to day 9; total dose 2.7 g; n = 40)

Lethality by at least 50% in the high-dose group compared with the low-dose group at day 28.

 

Government of the Amazonas State

Goldman, et al. [21]

US, Italy, Spain, Germany,

Hong Kong, Singapore, South Korea Taiwan

 

Open-label, RCT

62b

28

63.7%

200 mg of Remdesivir on day 1 followed by 100 mg of Remdesivir once daily for subsequent 4 or 9 days. All group receive a standard of care therapy according to the local guidelines.

5-day group (n = 200) and 10-day group (n = 197).

Clinical status on day 14, assessed on a 7-point ordinal scalea.

 

Gilead Sciences

Li Yueping, et al. [19]

China

Exploratory RCT, double-blind

49.4

21

46.5%

200 mg of Lopinavir boosted by 50 mg of Ritonavir (orally administered, twice daily 500 mg each time for 7-14 days; n = 34); 100 mg of Arbidol (orally administered, twice daily 200 mg three times for 7-14 days; n = 35);

Control group (n = 17)

Time of positive-to-negative conversion of SARS-CoV-2 nucleic acid from the initiation of treatment to day 21

 

IDSG; High-level Clinical Key Specialty (2019-2021)

Chen Zhaowei, et al. [3]

China

RCT, double-blind

44.7

6

46.8%

400 mg Hydroxychloroquine (HCQ) per day orally between days 1 and 5 (n = 31);

Standard of care (oxygen therapy, antiviral agents, antibiotic agents, and immunoglobulin, with or without corticosteroids; n = 31)

Time-to-clinical recovery (TTCR) at 5 days, defined as the return of body temperature and cough relief maintained for more than 72 h

 

Science and Technology Department of Hubei Province (2020FCA005)

 

Tang, et al. [26]

China

Open-label, RCT

46

28

55%

1200 mg Hydroxychloroquine (HCQ) daily for three days followed by a maintenance dose of 800 mg daily for the remaining days (two weeks for patients with mild to moderate disease and three weeks for those with severe disease; n = 75);

Standard of care (n = 75)

 

Negative conversion of SARS-CoV-2 by 28 days.

 

Emergent Projects of National Science and technology (2020YFCO844500)

Chen Chang, et al. [18]

China

Open-label, RCT

29.7c

7

46.6%

1600 mg of Favipiravir twice first day followed by 600 mg, twice daily, for the following days (n = 120);

200 mg of Arbidol, three times daily plus Standard of care (n = 120)

 

Clinical recovery rate at 7 days from beginning of treatment, defined as continuous (> 72 h) recovery of body temperature, respiratory rate, oxygen saturation and cough relief after treatment, with following quantitative criteria: axillary temperature 36.6 C, respiratory frequency 24 times/min, oxygen saturation 98% without oxygen inhalation; mild or no cough

NKRDPC (2020YFC0844400)

Hung, et al. [25]

Hong Kong

Open-label phase 2, RCT

 

52b

14

54%

400 mg of Lopinavir and 100 mg of Ritonavir every 12 h, 400 mg of Ribavirin every 12 h, 8 million international units of Interferon beta-1b on alternate days for 14 days (n = 86);

400 mg of Lopinavir and 100 mg of Ritonavir every 12 h for 14 days (41)

Time to providing a nasopharyngeal swab negative for SARS-CoV-2 by 7 days

Shaw-Foundation, Richard and Carol Yu, May Tam Mark Mei Yin, and Sanming Project of Medicine

Deftereos [4]

Greece

Open-label, RCT

 

64b

21

58.1%

1.5 mg of Colchicine followed by 0.5 mg 60 min later and maintenance doses of 0.5 mg twice daily (n = 56);

Standard of care (optimal medical treatment according to local protocols, as established by the National Public Health Organization and following the guideline of the European Centre for Disease Prevention and Control; n = 54)

Time from baseline to-clinical deterioration, defined as a grade increase on an ordinal clinical scalea

 

ELPEN, Acarpia, and Karian Pharmaceuticals companies

Huang [16]

China

RCT, phase 2, double-blind

 

14

59.1%

500 mg of Chloroquine orally twice daily for 10 days (n = 10);

400 mg of Lopinavir and 100 mg of Ritonavir orally twice daily for 10 days (n = 12);

Viral negative-transforming time and the negative conversion rate of SARS-CoV-2 RT-PCR at day 10, 14.

 

NR

Beigel [5]

US, UK, Denmark, Greece, Germany, Korea, Mexico, Spain, Japan, Singapore

RCT, double-blind

 

25

64.3%

200 mg on day 1, followed 100 mg daily for up to 9 additional days in single daily infusions of Remdesivir (n = 538); placebo (n = 521)

 

Time-to-recovery, defined as the first day, during the 28 days after enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category scalea

National Institute of Allergy and Infectious Disease

 

RCT: Randomized controlled trials; aDisease severity scale was defined as follow: 6-point, death; 5 points, hospitalization plus extracorporeal membrane oxygenation (ECMO) or invasive mechanical ventilation; 4 points, hospitalization plus noninvasive ventilation or high-flow supplemental oxygen; 3 points, hospitalization plus supplemental oxygen (not high-flow or noninvasive ventilation); 2 points, hospitalization plus supplemental oxygen; 1 point, hospital discharge; bMedian age; cProportion of patients aged 65 years or older; CIFMS: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; NDCD: new drug creation and development; CAMSEP: Chinese academy of Medical Sciences Emergency Project of Covid-19; NKRDPC: National key research and development program of China; BSTP: The Beijing science and technology project; IDSG: Infectious disease specialty of Guangzhou; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; NR: Not reported; RT-PCR: Real-time reverse-transcriptase polymerase-chain-reaction.