Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Molnupiravir vs Standard care/Placebo

Outpatients

Forest plots
(last update: 2022-11-04)

Summary of findings
(last update: 2022-11-22)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Molnupiravir
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.12 (1.07 - 1.18)	95 more per 1000 (from 56 more to 143 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Serious due to low number of participants/events
1 trials Koudinya Tippabhotla S, 2022 1220 participants		Molnupiravir 890 per 1,000 (851 - 938)	Standard care/Placebo 795 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death *	RR: 0.80 (0.56 - 1.15)	3 fewer per 1000 (from 6 fewer to 2 more)		High certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Not serious
5 trials Caraco Y, 2021; Jayk Bernal A, 2021; Koudinya Tippabhotla S, 2022; Khoo SH, 2022; Butler C, 2022 28766 participants		Molnupiravir 10 per 1,000 (7 - 15)	Standard care/Placebo 13 per 1,000
WHO progression score (level 7 or above) D28	RR: ( - )	Zero events in both groups		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious no events in both groups
2 trials Koudinya Tippabhotla S, 2022; Khoo SH, 2022 1400 participants		Molnupiravir 0 per 1,000 ( - )	Standard care/Placebo 0 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.27 (0.09 - 0.82)	1 fewer per 1000 (from 1 fewer to 0 fewer)		High certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Not serious
7 trials Koudinya Tippabhotla S, 2022; Caraco Y, 2021; Jayk Bernal A, 2021; Fischer W, 2021; Khoo SH, 2022; Butler C, 2022; Zou R, 2022 28999 participants		Molnupiravir 0 per 1,000 (0 - 1)	Standard care/Placebo 1 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
All-cause mortality D60	Outcome not yet measured or reported
Viral negative conversion D7	RR: 2.26 (0.86 - 5.97)	141 more per 1000 (from 16 fewer to 555 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns or high risk regarding adequate randomisation, deviation from intenden intervention, missing data and selection of the reported results Inconsistency: Very serious Inconsistency downgraded by 2 levels: I²=:97.4% Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
6 trials Koudinya Tippabhotla S, 2022; Jayk Bernal A, 2021; Fischer W, 2021; Khoo SH, 2022; Butler C, 2022; Zou R, 2022 3006 participants		Molnupiravir 252 per 1,000 (96 - 666)	Standard care/Placebo 112 per 1,000
Adverse events	RR: 0.99 (0.90 - 1.09)	3 fewer per 1000 (from 27 fewer to 24 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
6 trials Koudinya Tippabhotla S, 2022; Caraco Y, 2021; Jayk Bernal A, 2021; Fischer W, 2021; Khoo SH, 2022; Zou R, 2022 3216 participants		Molnupiravir 265 per 1,000 (241 - 292)	Standard care/Placebo 268 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Serious adverse events	RR: 0.89 (0.61 - 1.29)	1 fewer per 1000 (from 3 fewer to 2 more)		High certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Not serious
8 trials Kumarasamy N, 2022; Koudinya Tippabhotla S, 2022; Caraco Y, 2021; Jayk Bernal A, 2021; Fischer W, 2021; Khoo SH, 2022; Butler C, 2022; Zou R, 2022 30217 participants		Molnupiravir 8 per 1,000 (5 - 11)	Standard care/Placebo 8 per 1,000

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Hospitalized patients

Forest plots
(last update: 2022-09-15)

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=512

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
ChiCTR2200056817 Zou R, Front Pharm, 2022 Full text Commentary	Mixed	Molnupiravir	Standard care	RCT	Patients with confirmed COVID-19 (mild) isolated and treated by a single center in China	N=116	Some concerns Details	Full description
ISRCTN30448031; EudraCT: 2021-005748-31 PANORAMIC Butler C, SSRN, 2022 Full text Commentary	Public/non profit	Molnupiravir	Standard care	RCT	Outpatients with confirmed COVID-19 (mild-ambulatory) treated by multiple centers in the UK	N=25783	High Details	Full description
NCT04746183; ISRCTN27106947; EudraCT 2020-001860-2 AGILE CST-2 Khoo SH, medRxiv, 2022 Full text Commentary Commentary	Mixed	Molnupiravir	Placebo	RCT	Outpatients with confirmed COVID-19 (mild) treated by 5 centers in the UK	N=180	Some concerns Details	Full description
CTRI/2021/06/033938 Kumarasamy N, CROI, 2022 Full text	Private	Molnupiravir	Standard care	RCT	Outpatients with confirmed COVID-19 (mild) treated in 26 centers in India.	N=1218	Some concerns Details	Full description
CTRI/2021/07/034588 Koudinya Tippabhotla S, SSRN, 2022 Full text Commentary Commentary	Private	Molnupiravir	Standard care	RCT	Outpatients with confirmed COVID-19 (mild) treated at 16 centers in India	N=1220	Some concerns Details	Full description
NCT04575584 MOVe-IN Arribas J, N Engl J Med Evidence, 2021 Full text Commentary Commentary	Private	Molnupiravir 200mg	Placebo	RCT	Patients with suspeccted or confirmed COVID-19 (mild-moderate-severe) admitted to 65 centers in Brazil, Chile, Colombia, France, Israel, Mexico, Philippines, Poland, Russia, South Africa, South Korea	N=304	Some concerns Details	Full description
NCT04575597 MOVe-OUT Caraco Y, N Engl J Med Evidence, 2021 Full text Commentary	Private	Molnupiravir 200 Molnupiravir 400 Molnupiravir	Placebo	RCT	Outpatients with confirmed COVID-19 (asymptomatic, mild) treated by 82 centers in 14 countries	N=302	Low Details	Full description
NCT04575597 Jayk Bernal A, N Engl J Med, 2021 Full text Commentary	Private	Molnupiravir	Placebo	RCT	Outpatients with confirmed COVID-19 (mild-moderate) treated by 107 sites in 20 countries.	N=1433	Low Details	Full description
NCT04405570 Fischer W, Sci Transl Med, 2021 Full text Full text Commentary Commentary Commentary	Mixed	Molnupiravir 200 Molnupiravir 400 Molnupiravir	Placebo	RCT	Outpatients with confirmed COVID-19 (mild) treated by 10 centers in the USA	N=202	High Details	Full description