RECOVERY Trial: Randomized Evaluations of COVID-19 Therapies

Data were collected at study entry using a web-based case report form that included demographics and major comorbidities (appendix p 32). All eligible and consenting patients received usual standard of care and underwent an initial (main) randomisation comprising up to three parts in a factorial design (appendix pp 29–30): part 1, no additional treatment versus either dexamethasone, lopinavir–ritonavir, hydroxychloroquine, azithromycin, or colchicine; part 2, no additional treatment versus either convalescent plasma or REGN-COV2 (a combination of two monoclonal antibodies directed against SARS-CoV-2 spike protein); and part 3, no additional treatment versus aspirin. Over time, treatment groups were added to and removed from the protocol (appendix pp 26–29), and not all treatments were available at every hospital. Similarly, not all treatments were suitable for some patients (eg, owing to comorbid conditions or concomitant medication). In any of these cases, randomisation was between fewer groups.
Up to 21 days after the main randomisation and regardless of treatment allocation, RECOVERY trial participants with clinical evidence of progressive COVID-19 (defined as oxygen saturation <92% on room air or receiving oxygen therapy, and CRP ≥75 mg/L) could be considered for randomisation to tocilizumab versus usual care alone. Baseline data collected for this randomisation included amount of respiratory support, markers of progressive COVID-19 (including most recent oxygen saturation, CRP, ferritin, and creatinine result before second randomisation), suitability for the study treatment, and treatment availability at the site (appendix pp 33–34). For some patients, tocilizumab was unavailable at the hospital at the time of enrolment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. In such cases, the patients were not eligible for the tocilizumab randomisation. Patients with known hypersensitivity to tocilizumab, evidence of active tuberculosis infection or clear evidence of active bacterial, fungal, viral, or other infection (besides COVID-19) were not eligible for randomisation to tocilizumab.
Patients who were eligible for randomisation to tocilizumab were assigned to either usual standard of care or usual standard of care plus tocilizumab in a 1:1 ratio by means of web-based simple (unstratified) randomisation with allocation concealed until after randomisation. Allocated treatment was prescribed by the managing doctor. Roche Products (Welwyn Garden City, UK) supported the trial through provision of tocilizumab. Participants and local study staff were not masked to the allocated treatment. The steering committee, investigators, and all others involved in the trial were masked to the outcome data during the trial.