antiviral and associated therapy for COVID-19: living meta-analysis of clinical studies

Study explorer (study characteristics and results) method abbreviations pdf xlsx

display ongoing studies
Study	Ref.	Design	studied treatment	control treatment	patients	study risk of bias	sample sizes	Results
COVID 19 hospitalized meta-analysis
Patel ACTRN12620000454976			zinc	placebo	COVID 19 hospitalized	high	15/18	inconclusive
Tolouian			bromhexine	standard of care	COVID 19 hospitalized	high	59/52	no results
Abdulamir NCT04753619		RCT	niclosamide	standard of care	COVID 19 hospitalized	some concern	75/75	inconclusive
Ader (lopinavir/ritonavir plus interferon) NCT04315948		RCT	lopinavir/ritonavir plus interferon ß-1a	standard of care	COVID 19 hospitalized	some concern	145/148	safety concern	statistically significant 30 % decrease in clinical improvement,clinical improvement (time to event analysis only) with a moderate degree of certainty due to some concern in risk of bias statistically significant 86 % increase in serious adverse events with a moderate degree of certainty due to some concern in risk of bias statistically significant 3.4-fold increase in arrhythmia with a moderate degree of certainty due to some concern in risk of bias statistically significant 5.6-fold increase in elevated liver enzymes with a moderate degree of certainty due to some concern in risk of bias
DisCoVeRy (remdesivir) NCT04315948		RCT	remdesivir	standard of care	COVID 19 hospitalized	some concern	429/428	no results
Gaitan-Duarte (Rosuvastatin plus colchicine plus emtricitabine/tenofovir) NCT04359095		RCT	Emtricitabine/tenofovir plus colchicine plus rosuvastatin	standard of care	COVID 19 hospitalized	some concern	163/162	suggested	inconclusive 38 % decrease in deaths,death D28 (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 30 % decrease in mechanical ventilation with a moderate degree of certainty due to some concern in risk of bias
Mahajan		RCT	remdesivir	standard of care	COVID 19 hospitalized	some concern	41/41	inconclusive
Mobarak (DISCOVER) IRCT20200624047908N1		RCT	sofosbuvir and daclatasvir	placebo	COVID 19 hospitalized	NA	541/542	inconclusive	inconclusive 1 % increase in hospital discharge (PE)
Mobarak S (DISCOVER) IRCT20200624047908N		RCT	sofosbuvir and daclatasvir	placebo	COVID 19 hospitalized	some concern	541/542	inconclusive	inconclusive 3 % decrease in recovery (PE) with a moderate degree of certainty due to some concern in risk of bias
Sali		RCT	sofosbuvir	lopinavir/ritonavir	COVID 19 hospitalized	high	22/32	inconclusive
Ansarin IRCT202003117046797N		RCT	bromhexine	standard of care	COVID 19 hospitalized	high	39/39	suggested	inconclusive 91 % decrease in deaths (PE) but with a low degree of certainty due to high risk of bias suggested 91 % decrease in mechanical ventilation (PE) but with a low degree of certainty due to high risk of bias suggested 86 % decrease in ICU admission (PE) but with a low degree of certainty due to high risk of bias
Duke university HCQ-AZI NCT04335552		RCT	hydroxychloroquine plus macrolides	standard of care	COVID 19 hospitalized	NA	-/-	inconclusive
Gonzalez (IVER) NCT04391127		RCT	ivermectin	placebo	COVID 19 hospitalized	some concern	36/37	inconclusive
Lou Y ChiCTR2000029544		RCT	baloxavir marboxil	standard of care	COVID 19 hospitalized	some concern	10/10	inconclusive	inconclusive 88 % decrease in viral clearance by day 14 (PE) with a moderate degree of certainty due to some concern in risk of bias
NIH NIAID ACTT-1 NCT04280705		RCT	remdesivir	placebo	COVID 19 hospitalized	some concern	541/521	suggested	suggested 45 % decrease in deaths,deaths (time to event analysis only) with a moderate degree of certainty due to some concern in risk of bias suggested 29 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 35 % increase in clinical improvement (28-day) with a moderate degree of certainty due to some concern in risk of bias
Nojomi IRCT20180725040596N2		RCT	umifenovir (arbidol)	lopinavir/ritonavir	COVID 19 hospitalized	some concern	50/50	inconclusive
Nojomi IRCT20180725040596N2		RCT	lopinavir/ritonavir	umifenovir (arbidol)	COVID 19 hospitalized	some concern	50/50	inconclusive
RECOVERY NCT04381936		RCT	lopinavir/ritonavir	standard of care	COVID 19 hospitalized	some concern	1616/3424	inconclusive	inconclusive 3 % increase in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias the trial Steering Committee concluded that there is no beneficial effect of lopinavir-ritonavir in patients hospitalised with COVID-19 and closed randomisation to that treatment arm
RECOVERY (AZI, Horby) NCT04381936		RCT	azithromycin	standard of care	COVID 19 hospitalized	some concern	2582/5181	inconclusive	inconclusive 3 % decrease in deaths,deaths (time to event analysis only),death D28 (PE) with a moderate degree of certainty due to some concern in risk of bias
Sadeghi IRCT20200128046294N2		RCT	sofosbuvir and daclatasvir	standard of care	COVID 19 hospitalized	some concern	35/35	suggested	suggested 2.6-fold increase in clinical improvement (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
Sekhavati IRCT20200415047092N1		RCT	azithromycin	standard of care	COVID 19 hospitalized	some concern	56/55	inconclusive	inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
SOLIDARITY (lopi/rito) NCT04315948		RCT	lopinavir/ritonavir	standard of care	COVID 19 hospitalized	some concern	1399/1372	inconclusive	inconclusive 0 % increase in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
SOLIDARITY (remdesivir) NCT04315948		RCT	remdesivir	standard of care	COVID 19 hospitalized	some concern	2750/2725	inconclusive	inconclusive 5 % decrease in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
Yakoot DRKS00022203		RCT	sofosbuvir and daclatasvir	standard of care	COVID 19 hospitalized	some concern	44/45	suggested	suggested 60 % increase in recovery (PE) with a moderate degree of certainty due to some concern in risk of bias
COVID 19 all comers meta-analysis
Norwegian NOR study (remdesivir) NCT04321616		RCT	remdesivir	standard of care	COVID 19 all comers	some concern	43/58	no results
Chang Chen et al. ChiCTR2000030254		RCT	favipiravir	umifenovir (arbidol)	COVID 19 all comers	some concern	120/120	inconclusive	inconclusive 48 % increase in clinical improvement,clinical improvement (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
ELACOI (Standard of care) NCT04252885		RCT	umifenovir (arbidol)	standard of care	COVID 19 all comers	some concern	16/7	inconclusive
jRCTs041190120 jRCTs041190120		RCT	favipiravir	favipiravir	COVID 19 all comers	high	44/45	inconclusive	inconclusive 42 % increase in viral clearance ,viral clearance (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
Jun C NCT04252274		RCT	darunavir cobicistat	standard of care	COVID 19 all comers	high	15/15	inconclusive	inconclusive 42 % decrease in viral clearance by day 7 (PE) but with a low degree of certainty due to high risk of bias
Lou (FAVIPIRAVIR) ChiCTR2000029544		RCT	favipiravir	standard of care	COVID 19 all comers	some concern	10/10	inconclusive	inconclusive 82 % decrease in viral clearance ,viral clearance by day 14 (PE) with a moderate degree of certainty due to some concern in risk of bias
NCT04310228-FAVI (Zhao) ChiCTR2000030894		RCT	favipiravir	tocilizumab	COVID 19 all comers	some concern	-/-	inconclusive	inconclusive 68 % decrease in radiologic improvement (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
EPIC-SR unpublished NCT05011513		RCT	nirmatrelvir / ritonavir (Paxlovid)	placebo	COVID 19 all comers	NA	-/-	inconclusive
COVID-19 mild to moderate meta-analysis
I-TECH (Lim) NCT04920942		RCT	ivermectin	control	COVID-19 mild to moderate	some concern	241/249	inconclusive	inconclusive 25 % increase in clinical deterioration (PE) with a moderate degree of certainty due to some concern in risk of bias
Abd-Elsalam NCT04403555		RCT	ivermectin	control	COVID-19 mild to moderate	high	82/82	inconclusive
Babalola		RCT	ivermectin	lopinavir/ritonavir	COVID-19 mild to moderate	high	21/20	no results
Bukhari NCT04392713		RCT	ivermectin	standard of care	COVID-19 mild to moderate	high	50/50	suggested	suggested 10.6-fold increase in viral clearance by day 7 but with a low degree of certainty due to high risk of bias
FACCT Trial NCT04392973		RCT	favipiravir	standard of care	COVID-19 mild to moderate	some concern	125/129	inconclusive	inconclusive 15 % decrease in clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
Fontanesi NCT04348409		RCT	nitazoxanide	placebo	COVID-19 mild to moderate	NA	25/25	no results
Holubar M NCT04346628		RCT	favipiravir	placebo	COVID-19 mild to moderate	NA	75/74	inconclusive	inconclusive 24 % decrease in viral clearance ,viral clearance (time to event analysis only) (PE)
Kirti CTRI/2020/08/027225		RCT	ivermectin	placebo	COVID-19 mild to moderate	some concern	57/58	inconclusive	inconclusive 20 % decrease in viral clearance by day 7 (PE) with a moderate degree of certainty due to some concern in risk of bias
Rashad A (AZI vs SoC)		RCT	azithromycin	standard of care	COVID-19 mild to moderate	some concern	107/99	inconclusive
RIVET-COV (Mohan) (12mg and 24mg) CTRI/2020/06/026001		RCT	ivermectin	placebo	COVID-19 mild to moderate	high	104/52	inconclusive	inconclusive 10 % increase in viral clearance ,viral clearance by day 7 (PE) but with a low degree of certainty due to high risk of bias
Shenoy S NCT04529499		RCT	favipiravir	placebo	COVID-19 mild to moderate	high	175/178	inconclusive	inconclusive 1 % decrease in clinical improvement (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
Shinkai JapicCTI-205238		RCT	favipiravir	placebo	COVID-19 mild to moderate	some concern	107/49	safety concern	inconclusive 40 % increase in clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias statistically significant 18.5-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
Silva NCT04463264		RCT	nitazoxanide	placebo	COVID-19 mild to moderate	high	33/13	inconclusive
Solaymani-Dodaran IRCT20200318046812N1		RCT	favipiravir	lopinavir/ritonavir	COVID-19 mild to moderate	some concern	193/187	inconclusive
Ahmed		RCT	ivermectin	placebo	COVID-19 mild to moderate	high	48/24	suggested	suggested 3.1-fold increase in viral clearance (time to event analysis only),viral clearance by day 14 (PE) but with a low degree of certainty due to high risk of bias Paradoxically comparison of day 7 and 14 virological clearance between ivermectin doxycycline group vs placebo was not statistically significant (HR 2.3[0.6-9.0] and 1.7[0.8-4.0])
AVIFAVIR NCT04434248		RCT	favipiravir	standard of care	COVID 19 hospitalized, COVID-19 mild to moderate	some concern	20/20	suggested	suggested 2.9-fold increase in viral clearance ,viral clearance by day 7 (PE) with a moderate degree of certainty due to some concern in risk of bias Adverse drug reactions to AVIFAVIR were reported in 7/40 (17.5%) patients, including diarrhea, nausea, vomiting, chest pain and an increase in liver transaminase levels. The adverse drug reactions were mild to moderate and caused early discontinuation of the study drug in 2/40 (5.0%) patients.
Chaccour NCT04390022		RCT	ivermectin	placebo	COVID 19 outpatients, COVID-19 mild to moderate	low	12/12	inconclusive	inconclusive 8 % decrease in viral clearance ,viral clearance by day 7 (PE) with a high degree of certainty due to low risk of bias
Chachar NCT04739410		RCT	ivermectin	standard of care	COVID-19 mild to moderate	high	25/25	inconclusive	inconclusive 19 % increase in clinical improvement,clinical improvement (7-day) (PE) but with a low degree of certainty due to high risk of bias
COALITION I Covid-19 Brazil (AZI, Cavalcanti) NCT04322123		RCT	azithromycin	standard of care	COVID-19 mild to moderate	some concern	172/159	inconclusive	inconclusive 18 % decrease in clinical improvement,clinical improvement (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
Dabbous HM NCT04349241		RCT	favipiravir	standard of care	COVID-19 mild to moderate	some concern	50/50	inconclusive
ELACOI (Lopinavir/ritonavir) NCT04252885		RCT	umifenovir (arbidol)	lopinavir/ritonavir	COVID-19 mild to moderate	some concern	35/34	inconclusive	inconclusive 84 % increase in viral clearance by day 14 (PE) with a moderate degree of certainty due to some concern in risk of bias inconclusive 8 % increase in viral clearance by day 7 (PE) with a moderate degree of certainty due to some concern in risk of bias
ELACOI (lopinavir/ritonavir) NCT04252885		RCT	lopinavir/ritonavir	standard of care	COVID-19 mild to moderate	some concern	21/7	inconclusive
GS-US-540-5773 (Goldman) NCT04292899		RCT	remdesivir	remdesivir	COVID-19 mild to moderate	some concern	200/197	suggested	suggested 53 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias
GS-US-540-5774, 10 days NCT04292730		RCT	remdesivir	standard of care	COVID-19 mild to moderate	some concern	197/200	safety concern	suggested 58 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias suggested 88 % increase in clinical improvement (28-day) with a moderate degree of certainty due to some concern in risk of bias statistically significant 63 % increase in adverse events with a moderate degree of certainty due to some concern in risk of bias The primary endpoint was not met, no odds ratio is reported because the proportional odds assumption was not met
GS-US-540-5774, 5 days NCT04292730		RCT	remdesivir	standard of care	COVID-19 mild to moderate	some concern	199/200	conclusif	demonstrated 65 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
Hung et al. NCT04276688		RCT	lopinavir/ritonavir, ribavirin and interferon beta-1b	lopinavir/ritonavir	COVID-19 mild to moderate	some concern	86/41	conclusif	demonstrated 3.4-fold increase in viral clearance ,viral clearance (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 2.9-fold increase in clinical improvement,clinical improvement (time to event analysis only) with a moderate degree of certainty due to some concern in risk of bias
Khamis		RCT	favipiravir plus interferon	standard of care	COVID-19 mild to moderate	some concern	44/45	inconclusive
Krolewiecki NCT004381884		RCT	ivermectin	standard of care	COVID-19 mild to moderate	some concern	30/15	inconclusive
Li T NCT04273763		RCT	bromhexine	standard of care	COVID-19 mild to moderate	some concern	12/6	suggested	inconclusive 52 % decrease in clinical deterioration (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 9.0-fold increase in hospital discharge with a moderate degree of certainty due to some concern in risk of bias
NCT04542694 NCT04542694		RCT	favipiravir	standard of care	COVID-19 mild to moderate	some concern	100/100	suggested	suggested 1.1-fold increase in clinical improvement,clinical improvement (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 12.0-fold increase in viral clearance with a moderate degree of certainty due to some concern in risk of bias
Ren ChiCTR2000029853		RCT	azvudine	antiviral and associated therapy	COVID-19 mild to moderate	some concern	10/10	suggested	suggested 27.5-fold increase in viral clearance ,viral clearance by day 7 (PE) with a moderate degree of certainty due to some concern in risk of bias
Rocco NCT04552483		RCT	nitazoxanide	placebo	COVID-19 mild to moderate	high	238/237	inconclusive	inconclusive 19 % decrease in clinical improvement,clinical improvement (7-day) (PE) but with a low degree of certainty due to high risk of bias
Ruzhentsova T NCT04501783		RCT	favipiravir	standard of care	COVID-19 mild to moderate	some concern	112/56	suggested	suggested 63 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias inconclusive 28 % increase in viral clearance ,viral clearance (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 28 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias suggested 50 % increase in clinical improvement (7-day) with a moderate degree of certainty due to some concern in risk of bias
Shahbaznejad IRCT20111224008507N3		RCT	ivermectin	standard of care	COVID-19 mild to moderate	some concern	35/38	inconclusive
Udwadia CTRI/2020/05/025114		RCT	favipiravir	standard of care	COVID 19 hospitalized, COVID-19 mild to moderate	some concern	75/75	safety concern	inconclusive 37 % increase in viral clearance ,viral clearance (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 75 % increase in clinical improvement,clinical improvement (time to event analysis only),clinical improvement (28-day) with a moderate degree of certainty due to some concern in risk of bias suggested 94 % decrease in mechanical ventilation (time to event analysis only),mechanical ventilation with a moderate degree of certainty due to some concern in risk of bias statistically significant 5.4-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
COVID-19 severe or critically meta-analysis
Galan RBR-8h7q82		RCT	ivermectin	chloroquine and derivatives	COVID-19 severe or critically	some concern	53/115	suggested	inconclusive 6 % decrease in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 86 % decrease in mechanical ventilation with a moderate degree of certainty due to some concern in risk of bias
Galan RBR-8h7q82		RCT	ivermectin	hydroxychloroquine	COVID-19 severe or critically	some concern	53/115	suggested	inconclusive 6 % decrease in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 86 % decrease in mechanical ventilation with a moderate degree of certainty due to some concern in risk of bias
Cao ChiCTR2000029308		RCT	lopinavir/ritonavir	standard of care	COVID-19 severe or critically	some concern	99/100	suggested	inconclusive 31 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias suggested 94 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias
CAP-China (Wang et al.) NCT04257656		RCT	remdesivir	placebo	COVID-19 severe or critically	low	158/79	inconclusive	inconclusive 23 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a high degree of certainty due to low risk of bias
COALITION II Covid-19 Brazil (Furtado) NCT04321278		RCT	azithromycin	standard of care	COVID-19 severe or critically	some concern	214/183	safety concern	inconclusive 26 % decrease in clinical improvement,clinical improvement (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias statistically significant 6 % decrease in clinical improvement (7-day) with a moderate degree of certainty due to some concern in risk of bias
Okumuş NCT04646109		RCT	ivermectin	control	COVID-19 severe or critically	high	30/30	inconclusive
REMAP-CAP (lopinavir/ritonavir only) NCT02735707		RCT	lopinavir/ritonavir	standard of care	COVID-19 severe or critically	some concern	268/377	safety concern	statistically significant 17 % decrease in hospital discharge with a moderate degree of certainty due to some concern in risk of bias
REMAP-CAP (lopinavir/ritonavir plus hydroxychloroquine) NCT02735707		RCT	Lopinavir/ritonavir plus hydroxychloroquine	standard of care	COVID-19 severe or critically	some concern	29/377	safety concern	suggested 42 % decrease in deaths,deaths (time to event analysis only) with a moderate degree of certainty due to some concern in risk of bias statistically significant 37 % decrease in hospital discharge with a moderate degree of certainty due to some concern in risk of bias
21 studies excluded by filtering options (0 RCT / 21 OBS)

PE: primary endpoint; (a): to be demonstrated a result must be statistically significant on a primary endpoint (with multiplicity adjustment if necessary);
Study risk of bias assessed for the study primary endpoint(s) or the main endpoints in case of no formally defined primary endpoint(s).

Study explorer (study characteristics and results) method abbreviations pdf xlsx

COVID 19 hospitalized meta-analysis

COVID 19 all comers meta-analysis

COVID-19 mild to moderate meta-analysis

COVID-19 severe or critically meta-analysis