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

Abstract

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.

Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). 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 (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79).

Interpretation: In 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.

Figure 1

Trial profile *Number recruited overall during period that patients could be recruited into convalescent plasma comparison. †Reasons for exclusion are not mutually exclusive. ‡Patients in the group are not included in the analyses of this study. §5301 of 5795 patients with completed follow-up at time of analysis received convalescent plasma. ¶17 of 5763 patients with completed follow-up at time of analysis received convalescent plasma. ||A second randomisation to tocilizumab versus usual care in patients with hypoxia and C-reactive protein ≥75 mg/L was introduced in protocol version 4.0; 426 patients in the convalescent plasma group were randomly assigned to receive tocilizumab with 486 randomly assigned to receive usual care alone; 573 patients in the usual care group were randomly assigned to receive tocilizumab with 552 randomly assigned to receive usual care alone.

Figure 2

Effect of allocation to convalescent plasma on 28-day mortality

Figure 3

Effect of allocation to convalescent plasma on 28-day mortality by prespecified characteristics at randomisation The ethnicity, days since onset, and use of corticosteroids subgroups exclude those with missing data, but these patients are included in the overall summary. Information on use of corticosteroids was collected from June 18, 2020, onwards following announcement of the results of the dexamethasone comparison from the RECOVERY trial. RR=rate ratio.

Figure 4

Meta−analysis of mortality in RECOVERY and other trials O–E=observed–expected. Var=variance. RR=rate ratio.*Log−rank O−E for RECOVERY, O−E from 2 × 2 contingency tables for the other trials. RR is calculated by taking ln rate ratio to be (O−E)/V with normal variance 1/V, where V=Var (O–E). Subtotals or totals of (O−E) and of V yield inverse-variance weighted averages of the ln rate ratio values. †For balance, controls in the 2:1 studies count twice in the control totals and subtotals, but do not count twice when calculating their O−E or V values. Heterogeneity between RECOVERY and ten previous trials combined, χ²₁=2·7 (p=0·10).