Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
MOVe-OUT RCT, showing significantly lower risk of hospitalization or death. In subgroup analysis efficacy was much lower with the delta variant. NCT04575597 (history)
Discussion of concerns with this trial can be found at [defyccc.com, trialsitenews.com]
. See also: [, ]
.Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See [Fountain-Jones, Sanderson, ] for analysis of variants potentially created by molnupiravir.
risk of death, 89.0% lower, RR 0.11, p = 0.01, treatment 1 of 709 (0.1%), control 9 of 699 (1.3%), NNT 87.
risk of death/hospitalization, 30.4% lower, RR 0.70, p = 0.05, treatment 48 of 709 (6.8%), control 68 of 699 (9.7%), NNT 34, primary outcome.
risk of death/hosp. (gamma variant), 94.1% lower, RR 0.06, p = 0.004, treatment 0 of 37 (0.0%), control 9 of 47 (19.1%), NNT 5.2, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of death/hosp. (mu variant), 49.5% lower, RR 0.50, p = 0.15, treatment 6 of 75 (8.0%), control 13 of 82 (15.9%), NNT 13.
risk of death/hosp. (delta variant), 23.7% lower, RR 0.76, p = 0.41, treatment 18 of 237 (7.6%), control 22 of 221 (10.0%), NNT 42.
risk of death/hosp. (other variants), 42.2% lower, RR 0.58, p = 0.36, treatment 5 of 47 (10.6%), control 7 of 38 (18.4%), NNT 13.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Jayk Bernal et al., 16 Dec 2021, Randomized Controlled Trial, multiple countries, peer-reviewed, 22 authors, average treatment delay 4.0 days, trial NCT04575597 (history)
n e w e ng l a n d j o u r na l
m e dic i n e
Molnupiravir for Oral Treatment of Covid-19
in Nonhospitalized Patients
A. Jayk Bernal, M.M. Gomes da Silva, D.B. Musungaie, E. Kovalchuk, A. Gonzalez,
V. Delos Reyes, A. Martín‑Quirós, Y. Caraco, A. Williams‑Diaz, M.L. Brown, J. Du,
A. Pedley, C. Assaid, J. Strizki, J.A. Grobler, H.H. Shamsuddin, R. Tipping,
H. Wan, A. Paschke, J.R. Butterton, M.G. Johnson, and C. De Anda,
for the MOVe-OUT Study Group*
A BS T R AC T
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).
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.
The authors’ full names, academic degrees, and affiliations are listed in the
Appendix. Dr. De Anda can be contacted
at Merck, 309 Sumneytown Pike, North
Wales, PA 19454.
*The members of the MOVe-OUT study
group are listed in the Supplementary
Appendix, available at NEJM.org.
This article was published on December
16, 2021, at NEJM.org.
Copyright © 2021 Massachusetts Medical Society.
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, −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% confidence interval, −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.
Early treatment with molnupiravir reduced the risk of hospitalization or death in
at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and..
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