NCT04381936.

Study name	Randomised evaluation of COVID‐19 therapy (RECOVERY)
Methods	Trial design: multicentre, randomised adaptive trial Sample size: 12,000 Setting: inpatient Country: UK Language: English Number of centres: multiple (currently 176 active sites)
Participants	Inclusion criteria: Hospitalised SARS‐CoV‐2 infection (clinically suspected or laboratory‐confirmed) No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial Exclusion criteria: If the attending clinician believes that there is a specific contra‐indication to one of the active drug treatment arms (see Protocol Appendix 2; section 8.2 and Appendix 3; section 8.3 for children) or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial. Exclusion for CP randomisation: known moderate or severe allergy to blood components, Not willing to receive a blood product
Interventions	Intervention(s): randomised factorial assignment Main randomisation (part A): eligible patients will be randomly allocated between the available 5 treatment arms. No additional treatment vs lopinavir‐ritonavir vs low‐dose corticosteroids vs hydroxychloroquine vs azithromycin Main randomisation (part B): simultaneously, eligible patients will be randomly allocated between CP or no additional treatment Participants with progressive COVID‐19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second randomisation: no additional treatment vs tocilizumab Details of CP: Type of plasma: ABO‐identical if possible Volume: 275mLs +/‐ 75 mL Number of doses: 1‐2 Antibody‐titre:  NR Pathogen inactivated: NR  Treatment details, including time of plasma therapy (e.g. early stage of disease): hospitalised patients  Comparator: standard therapy and/or lopinavir‐ritonavir, low‐dose corticosteroids, hydroxychloroquine, azithromycin, tocilizumab Concomitant therapy: standard therapy and/or lopinavir‐ritonavir, low‐dose corticosteroids, hydroxychloroquine, azithromycin, tocilizumab Treatment cross‐overs: participants with progressive COVID‐19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second randomisation: no additional treatment vs tocilizumab. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated.
Outcomes	Primary study outcome: all‐cause mortality (time frame: within 28 days after randomisation) Primary review outcomes reported All‐cause mortality at hospital discharge: yes Time to death: yes Secondary review outcomes reported Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): yes (additional safety data will be collected in a subset of participants randomised to part B. These will be tabulated separately by allocation (CP vs no additional treatment): (i) sudden worsening in respiratory status; (ii) severe allergic reaction; (iii) temperature > 39 °C or ≥ 2 °C rise since randomisation; (iv) sudden hypotension, clinical haemolysis and thrombotic event) Number of participants with SAEs: yes Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: yes (within 28 days and up to 6 months after the main randomisation) 30‐day and 90‐day mortality: yes (up to 6 months after main randomisation) Admission on the ICU: NR Length of stay on the ICU: NR Time to discharge from hospital: yes QoL: NR Additional outcomes:  Need for renal replacement Development of new major cardiac arrhythmias
Starting date	19 March 2020
Contact information	Richard Haynes +44 (0)1865 743743 recoverytrial@ndph.ox.ac.uk
Notes	Recruitment status: recruiting Prospective completion date: June 2021 Sponsor/funding: University of Oxford