Efficacy and safety outcomes with remdesivir in COVID-19 patients: A meta-analysis

Table 1 General and baseline characteristics of included studies

Reference	Design	Study population	Total number of participants randomized/ completed	Age, mean ± SD years/median (IQR)	Male gender, %	Coexisting conditions, %	Severity status, %	Drug, dose and duration of interventions		Follow-up duration in d
								Remdesivir	Comparator
Beigel et al[14]	Double-blind, randomized, placebo-controlled trial	Hospitalized COVID-19 patients with evidence of lower respiratory tract involvement	Total: 1062/1025; Remdesivir: 541/517; Placebo: 521/508	Remdesivir: 58.6 ± 14.6; Placebo: 59.2 ± 15.4	Total: 64.4; Remdesivir: 65.1; Placebo: 63.7	Remdesivir: DM (30.8) HT (50.6); Placebo: DM (30.4); HT (50.9)	Remdesivir: MV or ECMO (24.2); Placebo: MV or ECMO (29.6)	Day 1: 200 mg iv loading dose on day 2-10: 100 mg iv daily	Placebo	29
WHO Solidarity Trial Consortium et al[15]	Open-labeled, randomized controlled Trial	Hospitalized COVID-19 patients	Remdesivir: 2750/2743; SC: 2725/2708	Remdesivir: NS; SC: NS	Total: 62.9; Remdesivir: 62.2; SC: 63.7	Remdesivir: DM (25.8); HD (20.8); Asthma (5.1); SC: DM (24.6); HD (20.9); Asthma (5.1)	Remdesivir: Ventilated (9.2); SC: Ventilated (8.6)	Day 1: 200 mg iv loading dose on day 2-10: 100 mg iv daily	SC	28
Spinner et al[20]	Open-labeled, randomized controlled Trial	Hospitalized moderate severity COVID-19 pneumonia patients	Total: 397/393; Remdesivir: 197/193; SC: 200/200	Remdesivir: 56 (45-66)1; SC: 57 (45-66)1	Remdesivir: 61; SC: 63	Remdesivir: DM (44); HD (58); HT (44); Asthma (16); SC: HT (41); Asthma (14); DM (38); HD (54);	Remdesivir: Supplemental oxygen (13); SC: Supplemental oxygen (19)	Day 1: 200 mg iv loading dose on day 2-10: 100 mg iv daily	SC	28
Wang et al[21]	Double-blind, randomized, placebo-controlled trial	Severe COVID-19 with pneumonia	Total: 237/226; Remdesivir: 158/150; Placebo: 79/76	Test: 66 (57-73)1; Placebo: 64 (53-70)1	Remdesivir: 56; Placebo: 65	Remdesivir: DM (25); HT (46); HD (9); Placebo: DM (21); HT (38); HD (3)	Remdesivir: Supplemental oxygen (100); Placebo: Supplemental oxygen (95)	Day 1: 200 mg iv loading dose on day 2-10: 100 mg iv daily	Placebo	28

¹Median (interquartile range). All patients received either remdesivir or placebo as an add-on to supportive care. DM: Diabetes mellitus; ECMO: Extracorporeal membrane oxygenation; HD: Heart disease; HT: Hypertension; IQR: Interquartile range; MV: Mechanical ventilation; NS: Not specified; SC: Supportive care; WHO: World Health Organization.

Table 2 Risk of bias assessment as per the Revised Cochrane risk of bias tool for randomized trials

Domain No.	Risk of bias domains	Beigel et al[14]	WHO Solidarity Trial Consortium et al[15]	Spinner et al[20]	Wang et al[21]
1	Risk of bias arising from the randomization process	Low	Low	Low	Low
2a	Risk of bias due to deviations from the intended interventions (effect of assignment to intervention)	Low	Low	Some concern	Low
2b	Risk of bias due to deviations from the intended interventions (effect of adhering to intervention)	Low	Low	Low	Low
3	Missing outcome data	Low	Low	Low	Low
4	Risk of bias in measurement of the outcome	Low	Low	Low	Low
5	Risk of bias in selection of the reported result	Low	Low	Low	Low
--	Overall risk of bias assessment	Low	Low	Some concerns	Low

WHO: World Health Organization.

Table 3 Quality assessment for efficacy and safety parameters as per the GRADE approach

No. of studies (design)	Limitation	Inconsistency	Indirectness	Imprecision	Publication bias	Quality	RR (95%CI)
Mortality
Four (RCT)	No serious limitations	Serious inconsistency (I2 = 59%)	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	0.83 (0.57-1.20)
Ventilation
Four (RCT)	No serious limitations	Serious inconsistency (I2 = 77%)	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	0.69 (0.41-1.18)
Composite Mortality and ventilation
Four (RCT)	No serious limitations	Serious inconsistency (I2 = 78%)	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	0.80 (0.58-1.11)
Clinical recovery
Three (RCT)	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	1.10 (1.04-1.16)
Adverse event
Three (RCT)	No serious limitations	Serious inconsistency (I2 = 77%)	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	1.05 (0.86-1.27)
Grade 3 or 4 adverse event
Three (RCT)	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	0.88 (0.79-0.99)
Serious adverse event
Three (RCT)	No serious limitations	No serious inconsistency	No serious indirectness	No serious imprecision	Asymmetric Funnel plot	Moderate	0.75 (0.63-0.89)

CI: Confidence interval; RCT: Randomized controlled trial; RR: Risk ratio.

Table 4 Sensitivity analysis of efficacy and safety outcomes based on the risk of bias assessment and study design

Variable	All studies		Sensitivity analysis(risk of bias assessment)		Sensitivity analysis (study design)
	RR (95%CI)	I2	RR (95%CI)	I2	RR (95%CI)	I2
Mortality	0.83 (0.57-1.20)	59	0.83 (0.55-1.26)	73	0.74 (0.38-1.44)	65
Ventilation	0.69 (0.41-1.18)	77	0.73 (0.42-1.27)	83	0.57 (0.41-0.77)	00
Composite mortality and ventilation	0.80 (0.58-1.11)	78	0.83 (0.60-1.16)	84	0.69 (0.55-0.86)	10
Clinical recovery	1.10 (1.04-1.16)	00	1.10 (1.02-1.18)	00	1.10 (1.02-1.18)	00
Adverse event	1.05 (0.86-1.27)	77	0.94 (0.86-1.02)	00	0.94 (0.86-1.02)	00
Grade 3 or 4 adverse event	0.89 (0.80-0.99)	00	0.87 (0.71-1.07)	10	0.87 (0.71-1.07)	10
Serious adverse event	0.75 (0.63-0.90)	00	0.76 (0.64-0.92)	00	0.76 (0.64-0.92)	00

CI: Confidence interval; RR: Risk ratio.