ABSTRACT
Background Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.
Methods The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.
Results 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).
Conclusions In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.
Trial registrations The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).
Funding Medical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).
Clinical Protocols
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Funding Statement
The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation and National Institute for Health Research (NIHR) (Grant reference MC PC 19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. TJ received funding from UK Medical Research Council (MC UU 0002-14). This report is independent research arising in part from Prof Jaki Senior Research Fellowship (NIHR-SRF-2015-08-001) supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care (DHCS).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The trial was conducted in accordance with the principles of the International Conference on Harmonization Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee (ref 20 EE 0101). Details of regulatory and independent ethics committee submissions are available on the study website: www.recoverytrial.net
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The protocol, consent form, statistical analysis plan, definition & derivation of clinical characteristics & outcomes, training materials, regulatory documents, and other relevant study materials are available online at www.recoverytrial.net This is a preliminary report and follow-up is ongoing. Data will be made available to bona fide researchers registered with an appropriate institution within 3 months of the final participant completing 28-day follow-up. As described in the protocol, the trial Steering Committee will facilitate the use of the study data and approval will not be unreasonably withheld. However, the Steering Committee will need to be satisfied that any proposed publication is of high quality, honours the commitments made to the study participants in the consent documentation and ethical approvals, and is compliant with relevant legal and regulatory requirements (e.g. relating to data protection and privacy). The Steering Committee will have the right to review and comment on any draft manuscripts prior to publication.
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