Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)

BackgroundSotrovimab is a neutralising monoclonal antibody that has been proposed as a treatment for patients admitted to hospital with COVID-19. MethodsIn this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 pneumonia. In the sotrovimab comparison, eligible and consenting patients were randomly allocated to either usual care alone or usual care plus a single 1g dose of sotrovimab, using web-based unstratified randomisation. Participants were retrospectively categorised according to their baseline serum SARS-CoV-2 nucleocapsid antigen concentration as high-antigen or low-antigen, using the median concentration as a cut-off. The primary outcome was 28-day mortality assessed by intention to treat. Secondary outcomes were time to discharge alive from hospital, and, among those not on invasive ventilation at baseline, progression to invasive ventilation or death. Recruitment closed on 31 March 2024 when funding ended. ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FindingsFrom 4 January 2022 to 19 March 2024, 1723 patients were recruited to the sotrovimab comparison. 720 (42%) were classified as high-antigen, 717 (42%) as low-antigen, and 286 (17%) had unknown antigen status. Over 80% of patients were vaccinated, over 80% had anti-spike antibodies at randomisation, and almost all were infected with Omicron variants. In the prespecified primary efficacy population of high-antigen patients, 82/355 (23%) allocated sotrovimab versus 106/365 (29%) allocated usual care died within 28 days (rate ratio 0.75; 95% CI 0.56-0.99; p=0.046). In an analysis of all randomised patients (regardless of antigen status), 177/828 (21%) allocated sotrovimab versus 201/895 (22%) allocated usual care died within 28 days (rate ratio 0.95; 95% CI 0.77-1.16; p=0.60). InterpretationIn patients hospitalised with COVID-19, sotrovimab was associated with reduced mortality in the primary analysis population of patients with a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population. FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).