Covid-19 Living Data

Trial NCT04746183; ISRCTN27106947; EudraCT 2020-001860-2
Publication AGILE CST-2 - Khoo SH, Lancet Infect Dis (2022) (published paper)
Dates: 2020-10-18 to 2022-03-16
Funding: Mixed (Ridgeback Biotherapeutics; Medical Research Council; the Wellcome Trust; UK National Institute of Healthcare Research; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections; UK Medical Research Council. Molnupiravir was provided by Ridgeback Biotherapeutics as 200mg capsules (with matching placebo).)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / UK Follow-up duration (days): 28
Inclusion criteria	Men and women Aged ≥18 years PCR-confirmed SARS-CoV-2 infection Within five days of symptom onset Free of uncontrolled chronic conditions Ambulant in the community Mild or moderate disease Women of childbearing potential and men were required to use two effective methods of contraception, one of which should be highly effective, throughout the study and for 50 and 100 days thereafter, respectively Participants were eligible irrespective of whether they were unvaccinated or had received one or multiple UK approved vaccines
Exclusion criteria	Pregnant or breastfeeding women Stage 4 and 5 (severe) chronic kidney disease Clinically significant liver dysfunction SpO2 <95% by oximetry or lung disease requiring supplementary oxygen ALT and/or AST >5 times upper limit of normal Platelets <50 × 109/L Experiencing any grade 3 or above Common Terminology Criteria for Adverse Events (CTCAE version 5) Previously reported hepatitis C infection Known allergy to any study medication Having received any other experimental agents within 30 days of first dose of study drug (use of other co-medications was allowed)
Interventions
	Treatment Molnupiravir 800 mg orally twice a day for 5 days
	Control Placebo
Participants
	Randomized participants : Placebo=90 Molnupiravir=90
	Characteristics of participants N= 180 Mean age : NR 77 males Severity : Mild: n= 180/ Asymptomatic: n=0 Number of vaccinated participants: 46
Primary outcome
	In the register EudraCT 2020-001860-27 - Master Protocol Co-primary endpoint: Pharmacodynamics of drug defined as time to negative viral titres in nose and/or throat swab, measured up to 29 days from randomisation. For CST-2 (EIDD-2801): To determine the safety and tolerability of multiple ascending doses of EIDD-2801. Efficacy Objective: To determine the ability of EIDD-2801 to improve viral clearance (time to negative PCR).
	In the report Time from randomisation to a negative SARS-CoV-2 PCR test
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 pre-print, the three trial registries, protocol and statistical analysis plan were used in data extraction and risk of bias assessment. The supplementary figures and tables referred to in the article were not available through the medRxiv pre-print webpage. The article reports on the molnupiravir sub-study of a platform trial. The primary and secondary outcomes in the article reflect those in the registry. The trial (n = 180) achieved its target sample size (n = 180). This study was updated on January 19th, 2023 with data extracted from the published report.