Covid-19 Living Data

Trial NCT04575597
Publication MOVe-OUT - Caraco Y, N Engl J Med Evidence (2021) (published paper)

Funding: Private (Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA, Brazil, Chile, Colombia, France, Germany, Israel, Russia, South Africa, Spain, Ukraine, UK Follow-up duration (days): 210
Inclusion criteria	Mild or moderate, laboratory confirmed Covid-19 with onset of Covid-19 signs and/or symptoms (hereafter termed “symptom onset”) up to (and including) 7 days before randomization Enrollment of participants with moderate Covid-19 was limited to no more than 50% of the total planned sample size All participants with mild Covid-19, and at least 75% of participants overall, were required to be at increased risk for severe illness from Covid-19. The following characteristics or underlying medical conditions, as adapted from the Centers for Disease Control and Prevention and the WHO,14,15 were protocol-defined factors that qualified a participant as being at increased risk: age older than 60 years, active cancer (other than minor cancers not associated with immunosuppression or significant morbidity/ mortality [e.g., basal cell carcinomas]), chronic kidney disease, chronic obstructive pulmonary disease, immunocompromised status/solid organ transplant recipient, obesity (body mass index 30 kg/m2), serious heart conditions (heart failure, coronary artery disease, and/or cardiomyopathies), diabetes mellitus, and sickle cell disease.
Exclusion criteria	Registry: Is currently hospitalized or is expected to need hospitalization for COVID-19 within 48 hours of randomization Is on dialysis or has reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 by the Modification of Diet in Renal Disease (MDRD) equation Has any of the following conditions: human immunodeficiency virus (HIV) with a recent viral load >50 copies/mL (regardless of CD4 count) or an AIDS-defining illness in the past 6 months, participants with HIV may only be enrolled if on a stable antiretroviral therapy regimen a neutrophilic granulocyte absolute count <500/mm^3 Has a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) with cirrhosis, end-stage liver disease, hepatocellular carcinoma, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X upper limit of normal at screening Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days prior to randomization Is taking or is anticipated to require any prohibited therapies Is unwilling to abstain from participating in another interventional clinical study through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to: participants who are not expected to survive longer than 48 hours after randomization, or participants with a recent history of mechanical ventilation, or participants with conditions that could limit gastrointestinal absorption of capsule contents.
Interventions
	Treatment Molnupiravir 800 mg twice daily for 5 days Molnupiravir 400 400 mg twice daily for 5 days Molnupiravir 200 200 mg twice daily for 5 days
	Control Placebo
Participants
	Randomized participants : Placebo=74 Molnupiravir=76 Molnupiravir 400=77 Molnupiravir 200=75
	Characteristics of participants N= 302 Mean age : NR 159 males Severity : Mild: n= 282/ Asymptomatic: n=7 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 ] Go to 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 associatedwith 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 6days ] An AE is any untoward medical occurrence in a clinical study participant, temporally associatedwith
	In the report Adverse event (AE) data collection by the investigator from the time of randomization through 14 days after cessation of treatment, physical examinations (including vital signs), and laboratory tests (hematology and chemistry).; The proportion of participants who were hospitalized and/or died from any cause through day 29.
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 protocol and study registry were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome does reflect the reported primary outcome.