Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on hydroxychloroquine, 26 May 2020
Prof Peter Horby and Prof Martin Landray, Chief Investigators of the RECOVERY Trial, said ‘We have been working over the weekend to understand the implications of the Mehra paper for the safety and welfare of patients randomised to hydroxychloroquine.
‘On Saturday 23 May, the independent Data Monitoring Committee conducted an urgent review of the data that we have collected so far on the effects of hydroxychloroquine on mortality among patients admitted to hospital with COVID-19. The Committee concluded that there is “no cogent reason to suspend recruitment for safety reasons.”
‘The Committee found that the effects of hydroxychloroquine on mortality reported in the analysis by Mehra were not consistent with those observed in the RECOVERY Trial. The Committee therefore recommended that the trial continue recruitment without interruption, a recommendation that was endorsed on Sunday by the MHRA.
‘The conclusion of the Mehra paper is that “Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients.” The RECOVERY Trial is currently the largest randomised controlled trial of hydroxychloroquine and other potential treatments for COVID-19. Enrolment in this trial is the best way to provide definitive evidence on these drugs.’
The letter we received from the independent Data Monitoring Committee and our letter to study investigators are available on the homepage of the RECOVERY Trial website, www.recoverytrial.net.
A range of potential treatments have been suggested for COVID-19 but nobody knows if any of them will turn out to be more effective in helping people recover than the usual standard of hospital care which all patients will receive.
The RECOVERY Trial is a large, randomised controlled trial of possible treatments for patients admitted to hospital with COVID-19. Over 10,000 patients have been randomised to the following treatment arms, or no additional treatment:
- Lopinavir-Ritonavir (commonly used to treat HIV)
- Low-dose Dexamethasone (a type of steroid, which is used in a range of conditions typically to reduce inflammation)
- Hydroxychloroquine (related to an anti-malarial drug)
- Azithromycin (a commonly used antibiotic)
- Tocilizumab (an anti-inflammatory treatment given by injection)
From 26 May 2020, the trial is also assessing the impact of convalescent plasma (collected from donors who have recovered from COVID-19 and contains antibodies against the SARS-CoV-2 virus).
- There have been two recent observational analyses of the use of hydroxychloroquine (HCQ) for treatment of COVID-19. One reported no significant effect on the outcome of intubation or death (Geleris et al, New Engl J Med 7 May 2020), while the other reported a hazard ratio of 1.33 for all-cause mortality (Mehra et al, Lancet 22 May 2020). The authors of both papers conclude that their findings should be interpreted with caution, are not definitive, and that randomised controlled trials are required to reach any conclusion about the benefit or harm of HCQ for COVID-19.
- In response to the letter provided by MHRA, the Chair of the independent DMC conducted an urgent review of unblinded data for the HCQ vs. Standard of Care comparison within RECOVERY. Following an initial review by the DMC Chair and further discussions between the RECOVERY Chief Investigators and the MHRA, the independent Data Monitoring Committee then held a full meeting by videoconference and issued a letter indicating that, “the Data Monitoring Committee saw no cogent reason to suspend recruitment for safety reasons and recommended the trial continue recruitment without interruption.”
- Given the additional review of unblinded data conducted by the full independent Data Monitoring Committee and their recommendation to continue without interruption, it is the view of the Chief Investigators that any pause in recruitment would be unjustified and would not be in the interests of trial participants or public health.
- The RECOVERY Trial provides the best and most rapid opportunity to produce robust information on the overall effects of HCQ on the risk of death from COVID-19. These results will be of huge importance to the millions of patients who are (or will be) treated with HCQ and could have a major impact on a disease that has already caused hundreds of thousands of deaths.
- In the light of the information provided in this response, and the ongoing monitoring of the safety of hydroxychloroquine by the independent Data Monitoring Committee, the MHRA has confirmed in writing that “it is acceptable to allow continued randomisation into the hydroxychloroquine arm of the trial.”
- The RECOVERY Trial therefore continues as planned, with no alteration to the protocol, and all treatment arms remain open to enrolment.