Covid-19 Living Data

Trial NCT02735707
Publication Estcourt L, JAMA, 2021 (published paper)
Dates: 2020-05-05 to 2021-01-18
Funding: Mixed (PREPARE consortium by the European Union; Australian National Health and Medical Research Council; Australian Medical Research Future Fund; New Zealand Health Research Council; Canadian Institutes of Health Research COVID-19 Rapid Research Funding; Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant; NIHR; UK NIHR; NIHR Imperial Biomedical Research Centre; Health Research Board of Ireland; UPMC Learning While Doing Program; Translational Breast Cancer Research Consortium; Pittsburgh Foundation; French Ministry of Health; Minderoo Foundation; Wellcome Trust Innovations Project; Australian government; DHSC; EU SoHo Grants)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Australia, Canada, UK, USA Follow-up duration (days): 90
Inclusion criteria	Patients aged 18 years or older; confirmed SARS-CoV-2 infection; admitted to hospital; classified as moderately or severely ill were eligible for enrollment in the Covid-19 Immunoglobulin Domain, equivalent to severely or critically ill respectively, as per the World Health Organization (WHO) case definitions.
Exclusion criteria	Presumption that death was imminent with lack of commitment to full support; participation in REMAP-CAP in the prior 90 days; known hypersensitivity to convalescent plasma; objection to receiving plasma products; previous history of transfusion-related acute lung injury (TRALI); and more than 48h elapsed since ICU admission or 14 days since hospital admission.
Interventions
	Treatment Standard care *
	Control Convalescent plasma ( / )
Participants
	Randomized 2000 participants (n₁=916 / n₂= 1084)
	Characteristics of participants N=2000 Mean age : 60.2 1345 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=1336 Critical: n=648
Primary outcome
	In the register 1. All-cause mortality [ Time Frame: Day 90 ] 2. Days alive and not receiving organ support in ICU [ Time Frame: Day 21 ] Primary end-point for patients with suspected or proven COVID-19 pandemic infection
	In the report Respiratory and cardiovascular organ support-free days up to day 21
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated 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 pre-print, study registry and protocol were used in data extraction and risk of bias assessment. The report contains convalescent plasma vs mask data from the Immunoglobulin domain of the REMAP-CAP clinical trial (an international, adaptive platform trial). This arm of the trial was terminated due to futility. Quote: "At a scheduled adaptive analysis, the statistical trigger for futility in critically ill participants with Covid-19 was met (posterior probability of futility 96.4%, (OR 0.95, 95% Credible Interval (CrI) 0.73 to 1.23). Assignment to this domain closed on January 11, 2021 for critically ill participants (randomization continued for participants who were not critically ill). After announcement of the preliminary RECOVERY trial results on January 15,2021, the ITSC halted recruitment to all patients within the domain" There was some discrepancy between the report and the protocol as it pertains to time to death. The protocol pre-specifies this outcome as "ICU mortality censored at 90 days". There were no important changes from the trial registration in the population, intervention, or control treatments. Some outcomes from the registry are not reported in the paper (e.g., All cause mortality) and some outcomes in the report were not specified in the registry (e.g., Serious adverse events). Mortality extracted is in-hospital mortality. Critically ill participants (using WHO definitions of severity) comprised the main analysis, while severe participants were used for borrowing in statistical models. The study was updated on November 11th, 2021 with data from the peer-reviewed publicaiton.