Covid-19 Living Data

Trial NCT04589949, NCT04621123
Publication COMPILE home - Millat-Martinez P, medRxiv (2021) (preprint)
Dates: 2020-11-01 to 2021-07-13
Funding: Mixed (ZONMW (the Netherlands), SUPPORT-E, YoMeCorono, The Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A.)
Conflict of interest: No

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Netherlands, Spain Follow-up duration (days): 28
Inclusion criteria	Participant of a trial that joined the COMPILEhome consortium Confirmed COVID-19 diagnosis by a diagnostic PCR or antigen test Neither hospitalized nor at the emergency room department of a hospital before or at the time of randomization Symptomatic with illness onset ≤7 days at the time of screening for the study Age 50 or older Trials had to be approved by the institutional review boards, and competent authorities of the countries involved All patients gave written informed consent.
Exclusion criteria	Life expectancy <28 days in the opinion of the treating physician (CoV-Early only) unable to provide written informed consent History of allergic reactions to blood or plasma products or methylene blue Known IgA deficiency History of previous confirmed SARS-CoV-2 infection, significantly abnormal liver function (Child Pugh C), CKD ≥ stage 4, or need of dialysis treatment, pre-existing condition that increases risk of thrombosis (COnV-ert only).
Interventions
	Treatment Convalescent plasma 200-300 mL IV infusion once-off
	Control Placebo Non-convalescent plasma (CoV-Early) or 0.9% saline solution (COnV-ert)
Participants
	Randomized participants : Convalescent plasma=398 Placebo=399
	Characteristics of participants N= 797 Mean age : NR 522 males Severity : Mild: n= 797/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register CoV-Early trial: Highest disease status [ Time Frame: 28 days following transfusion of convP or FFP ] Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group; COnV-ert trial: 1) Hospitalization rate (safety and efficacy) [ Time Frame: Day 28 ] Assess the therapeutic potential of early administration of convalescent MBT plasma in reducing the rate of hospitalization in non-hospitalised mild or moderate COVID-19 patients; 2)SARS-CoV-2 viral load (safety and efficacy) [ Time Frame: Day 7 ] Assess the therapeutic potential of early administration of convalescent MBT plasma in reducing SARS-CoV-2 viral load at day 7, measured by quantitative RT-PCR (RT-qPCR) in non-hospitalised mild or moderate COVID-19 patients.
	In the report A 5-point disease severity scale (fully recovered by day 7 or not, hospital or ICU admission and death) and a composite of hospitalization or death.
Documents available	Protocol NR Statistical plan NR 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	Some concerns
General comment	In addition to the pre-print article, the trial registries and supplementary appendices were used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The article reports the results of two similar trials (CoV-Early and COnV-ert), which started to pool outcome data when less than 20% of their target sample sizes had been randomized, and whose study teams agreed upon a minimal set of data required to analyze the primary and secondary endpoints. The co-primary outcomes in the article reflect the primary outcome in one trial registry and a secondary outcome in the other. The trials (n = 797) did not achieve their combined target sample sizes (n = 1,164) due to early termination of recruitment because of increasing uptake of vaccinations and recommendations for use of monoclonal antibodies.