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 ³ 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.