It is the worlds largest randomized clinical trial of potential coronavirus treatments. As of this morning (Friday May 8th), 9418 participants have been randomized at 173 sites in the UK. What is even more astounding is that the first draft of the protocol was March 10th. It was submitted to both the Regulatory authorities (MHRA) and the Ethics Committee (IRB) on March 13th. It received regulatory approval on March 16th and IRB approval on March 18th. The first patient was enrolled on March 19th. By April 1st, 1000 patients had been enrolled.
The study Sponsor is the University of Oxford and it is being funded by UK Research and Innovation/ National Institute of Health Research.
In line with quality by design principles, all trial processes are greatly streamlined. The main outcomes are death, discharge, the need for ventilation and the need for renal replacement therapy.
The ICF is simple (~ 4 pages including the signature lines). The trial is designed to minimize the burden on front line hospital staff. Eligibility criteria are straightforward: aged 18, hospitalized and known or strongly suspected case of SARS-COV-2 infection, and no medical history that might put the patient at significant risk. Trial processes including paperwork are minimized. There is a baseline case report form page which the clinician completes prior to randomizing the patients. A second case report form follow up page is completed when the patient is discharged, dies or at 28 days after randomization, whichever comes sooner.
Initial randomization is to one of four arms: usual care, usual care plus lopinavir-ritonavir, usual care plus low-dose corticosteroids, usual care plus hydroxychloroquine or usual care plus azithromycin. There is a second randomization for patients who deteriorate after entry into the trial (evidence of a hyper-inflammatory state). They can be randomized to usual supportive care or Tocilizumab (a rheumatoid arthritis drug).
For patients for whom not all trial arms are appropriate or at locations where not all drug agents are available, randomization is between fewer arms.
It is an adaptive design. There is an independent Data Monitoring Committee who will assess whether the randomized comparisons in the study have provided evidence on mortality that is strong enough to affect national and global treatment strategies. They will inform the Trial Steering Committee who will make the results available to the public and amend trial arms accordingly. New trial arms can be added as evidence emerges about other candidates that should be evaluated.
The investigators appear to have thought of everything. The processes are all completed on-line. You can download the protocol and look at the CRF pages as well as the consent at: https://www.recoverytrial.net/
Look what can be accomplished when great minds collaborate and the will is there to overcome hurdles.