Trial NCT04381936; EudraCT 2020-001113-21; ISRCTN5018967
Publication Horby P, Lancet, 2021 (published paper)
Dates: 2020-05-28 to 2021-01-15
Funding: Public/non profit (UK Research and Innovation (Medical Research Council) and National Institute of Health Research )
Conflict of interest: No

Methods
RCT
Blinding: Unblinded
Location : Multicenter / UK
Follow-up duration (days): 28
Inclusion criteriaHospitalised patients; any age; clinically suspected or laboratory-confirmed SARS-CoV-2 infection; no medical history that might, in the opinion of the attending clinician, put them at significant risk if they were to participate in the trial.
Exclusion criteriaFor some patients, convalescent plasma was either declined, unavailable at the trial site at the time of enrolment, or considered in the opinion of the attending doctor to be definitely contraindicated (e.g. known moderate or severe allergy to blood components or unwilling to receive a blood product). These patients were ineligible for randomisation to the comparison of convalescent plasma versus usual care.
Interventions
Treatment
Convalescent plasma
275 ml (+/-75 ml) IV infusion; two doses at least 12 hours apart (D1 and D2)
Control
Standard care ( / )
Definition of Standard care: *
Participants
Randomized
11558 participants (n1=5795 / n2= 5763)
Characteristics of participants
N=11558
Mean age : 63.5
7430 males
Severity : Mild: n=897 / Moderate: n=*/ Severe: n=* Critical: n=617
Primary outcome
In the register
All-cause mortality [Time Frame: Within 28 days after randomisation].
In the report
28-day all-cause mortality
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
Some concerns
General comment In addition to all available versions of the published/pre-print article, the study registries, statistical analysis plan, protocol and supplementary appendix were used in data extraction and risk of bias assessment. This study reported here is part of the RECOVERY trial (an investigator-initiated, individually randomized, controlled, open-label, adaptive platform trial to evaluate the effects of potential treatments in patients hospitalized with COVID-19. The trial was conducted at 176 National Health Service (NHS) hospital organizations in the United Kingdom). There were no substantive differences in study procedures, population, interventions and outcomes between the pre-print article and the trial registries, study protocol and statistical analysis plan. The study achieved its pre-stated sample size. The study arm was terminated early due to insufficient efficacy. Enrolment was closed on 15th January 2021 and preliminary results made available.
Quote: "On 7th January 2021, the independent data monitoring committee (DMC) conducted a routine review of the data and recommended that the chief investigators pause the recruitment to the convalescent plasma comparison in those patients receiving invasive mechanical ventilation (including extracorporeal membrane oxygenation) at the time of randomisation. At the same time, the DMC recommended that recruitment to the convalescent plasma comparison continue for all other eligible patients.
On 14th January 2021, the DMC conducted another routine review of the data and notified the chief investigators that there was no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any pre-specified subgroup. The DMC therefore recommended that recruitment to the convalescent plasma portion of the study should cease and follow-up be completed. Enrolment of patients to the convalescent plasma group was closed on 15th January 2021 and the preliminary result for the primary outcome was made public." On 18th of May, 2021, this study was updated based on the published report.