Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Abstract

Background

Treatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality.

Findings

Between 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1·00; 95% confidence interval [CI] 0·93 to 1·07; p=0·93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66% vs . 67%; rate ratio 0·98; 95% CI 0·94-1·03, p=0·50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28% vs . 29%; rate ratio 0·99; 95% CI 0·93-1·05, p=0·79).

Interpretation

Among patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant refs: MC_PC_19056; COV19-RECPLA).

SciScore for 10.1101/2021.03.09.21252736: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	IRB: The trial is conducted in accordance with the principles of the International Conference on Harmonisation–Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee (ref: 20/EE/0101). Consent: Written informed consent was obtained from all patients or from their legal representative if they were too unwell or unable to provide consent.
Randomization	Randomisation was web-based simple (unstratified) randomisation with allocation concealment (appendix pp 33-34).
Blinding	12 Consequently, while still blind to the results of the trial, the RECOVERY steering committee determined that the trial should enrol sufficient patients to provide at least 90% power at a two-sided p-value of 0.01 to detect a proportional reduction in 28-day mortality of one-fifth among those patients with and, separately, without detectable SARS-CoV-2 antibodies at randomisation (appendix p 34).
Power Analysis	12 Consequently, while still blind to the results of the trial, the RECOVERY steering committee determined that the trial should enrol sufficient patients to provide at least 90% power at a two-sided p-value of 0.01 to detect a proportional reduction in 28-day mortality of one-fifth among those patients with and, separately, without detectable SARS-CoV-2 antibodies at randomisation (appendix p 34).
Sex as a biological variable	(Through the play of chance, a slightly lower proportion of males were allocated convalescent plasma than usual care; analyses adjusted for sex are provided in the appendix [webtable 7] and are virtually identical to the main results shown.

Table 2: Resources

Antibodies
Sentences	Resources
Eligible and consenting patients were allocated in a ratio of 1:1:1 to either usual care, usual care plus convalescent plasma or (from 18 September 2020) usual care plus REGN-COV2 (a combination of two monoclonal antibodies directed against SARS-CoV-2 spike protein).	SARS-CoV-2 spike protein). suggested: None
Prespecified analyses of the primary outcome were performed in seven subgroups defined by characteristics at randomisation: age, sex, ethnicity, level of respiratory support received, days since symptom onset, use of systemic corticosteroids, and presence of anti-SARS-CoV-2 antibody.	anti-SARS-CoV-2 suggested: None

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

Identifier	Status	Title
NCT04381936	Recruiting	Randomised Evaluation of COVID-19 Therapy

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
No funding statement was detected.
No protocol registration statement was detected.

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