Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Abstract

Background: Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.

Methods: In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m2, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings: Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).

Interpretation: In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

Funding: UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.

Conflict of interest statement

Declaration of interests We declare no competing interests.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Trial profile Of the 11 340 patients randomly assigned to receive colchicine or usual care, 7091 (63%; 3505 [62%] of the colchicine group vs 3586 [63%] of the usual care group) patients were additionally randomised to receive convalescent plasma or REGN–COV2 or usual care; 7545 (67%; 3747 [67%] of the colchicine group vs 3798 [66%] of the usual care group) patients were additionally randomised to receive aspirin or usual care; and 1635 (14%; 802 [14%] of the colchicine group vs 833 [15%] of the usual care group) patients were additionally randomised to receive baricitinib or usual care. *Number recruited overall during period that adult participants could be recruited into colchicine comparison. †Colchicine unavailable and colchicine unsuitable groups are not mutually exclusive. ‡5122 (93%) of 5510 patients with completed follow-up at time of analysis received colchicine. §20 (<1%) of 5605 patients with completed follow-up at time of analysis received colchicine. ¶Includes 251 (4%) of 5610 patients in the colchicine group and 306 (5%) of 5730 patients in the usual care group allocated to receive tocilizumab.

Figure 2

Effect of allocation to colchicine on 28-day mortality

Figure 3

Effect of allocation to colchicine on 28-day mortality by baseline characteristics Ethnicity, days since onset, and use of corticosteroids subgroups exclude those with missing data, but these patients are included in the overall summary.