Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients.
Open accessAbstract
BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).
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Most outpatient antiviral trials for COVID-19 have enrolled only participants who were within five days of symptom onset.
“Most outpatient COVID-19 antiviral trials have limited enrollment to participants within 5 days of symptom onset.1,2”
From Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial (2023) · cites this paper as [1]
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- Authors
- Jayk Bernal, A., Gomes da Silva, M. M., Musungaie, D. B., Kovalchuk, E., Gonzalez, A., Delos Reyes, V., Martín-Quirós, A., Caraco, Y., Williams-Diaz, A., Brown, M. L., Du, J., Pedley, A., Assaid, C., Strizki, J., Grobler, J. A., Shamsuddin, H. H., Tipping, R., Wan, H., Paschke, A., Butterton, J. R., Johnson, M. G., & De Anda, C.
- Affiliations
- IMAT Oncomédica, Monteria, Colombia
- Department of Public Health, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil
- Jongaie Research, Pretoria, South Africa
- Medical Research Institute LLC, Saint Petersburg, Russia
- Advanced Research For Health Improvement LLC, Immokalee, FL, USA
- Lung Center of the Philippines, Quezon City, Philippines
- Hospital Universitario La Paz - IdiPAZ, Madrid, Spain
- Hadassah Medical Center (IL)
- Merck & Co., Inc., Kenilworth, NJ, USA
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-02-10
- Volume
- 386
- Issue
- 6
- Pages
- 509-520
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8693688
- OpenAlex
- W4200051875
- Cited by
- 1,857
- References
- 34
- Citations by year
- 2026: 95 · 2025: 205 · 2024: 303 · 2023: 564 · 2022: 677 · 2021: 10 · 2020: 1
- FWCI
- 123.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Merck
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- molnupiravir, COVID-19 pandemic, SARS-CoV-2, oral antiviral therapy, non-hospitalized patients, risk factors for severe COVID-19, unvaccinated adults, small-molecule antivirals, drug safety, adverse events, interim analysis, subgroup analysis, prior SARS-CoV-2 infection
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Antiviral Agents, Cytidine, Double-Blind Method, Female, Humans, Hydroxylamines, Male, Middle Aged, Treatment Outcome, Viral Load, Young Adult
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