Trial NCT04575597
Publication Jayk Bernal A, N Engl J Med (2021) (published paper)
Dates: 2021-05-06 to 2021-10-02
Funding: Private (Merck Sharp and Dohme)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Argentina, Brazil, Canada, Chile, Colombia, Egypt, France, Germany, Guatemala, Italy, Japan, Mexico, Philippines, Russian Federation, South Africa, Sp
Follow-up duration (days): 28
Inclusion criteria
  • Non-hospitalized adults with mild or moderate Covid-19
  • SARS-CoV-2 infection that had been laboratory-confirmed no more than 5 days earlier
  • Onset of signs or symptoms no more than 5 days earlier
  • At least one sign or symptom of Covid-19
  • At least one risk factor for development of severe illness from Covid-19 (age >60 years, active cancer, chronic kidney disease, chronic obstructive pulmonary disease, obesity, defined by a body-mass index [the weight in kilograms divided by the square of the height in meters] ≥30, serious heart conditions [heart failure, coronary artery disease, or cardiomyopathies], or diabetes mellitus)
Exclusion criteria
  • An anticipated need for hospitalization for Covid-19 within the next 48 hours
  • Dialysis or estimated glomerular filtration rate less than 30 ml per minute per 1.73 m2
  • Pregnancy
  • Unwillingness to use contraception during the intervention period and for at least 4 days after completion of the regimen
  • Severe neutropenia (absolute neutrophil count of <500 per milliliter)
  • Platelet count below 100,000 per microliter
  • SARS-CoV-2 vaccination
Interventions
Treatment
Molnupiravir
800 mg orally twice a day for 5 days
Control
Placebo

Participants
Randomized
participants :
Molnupiravir=716
Placebo=717
Characteristics of participants
N= 1433
Mean age : NR
698 males
Severity : Mild: n= 785/ Asymptomatic: n=0
Number of vaccinated participants: NR
Primary outcome
In the register
1) Percentage of participants who are hospitalized and/or die [ Time Frame: Up to 29 days ] Hospitalization (all cause) is ≥24 hours of acute care in a hospital or similar acute care facility. Death is due to any cause. 2) Percentage of participants with an adverse event (AE) [ Time Frame: Up to ~7 months ] An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 3) Percentage of participants who discontinued study intervention due to an AE [ Time Frame: Up to 6 days ] An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
In the report
1) the incidence of hospitalization for any cause (defined as ≥24 hours of acute care in a hospital or any similar facility) or death through day 29 2) the incidence of adverse events
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Low
General comment In addition to the published article, the trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. There is no change from the trial registration in the intervention and control treatments. The primary outcomes described in the article generally reflect those in the registry, with the omission of the percentage of participants who discontinued study intervention due to an AE. Recruitment was terminated on the basis of positive efficacy results from a planned interim analysis performed when 50% of target enrollment had been followed through day 29, and thus the study (n = 1433) did not achieve its target sample size (n = 1550).