Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial

Authors

Tayyab Shah, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Marianne McCarthy, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Irem Nasir, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Herb Archer, Yale New Haven Health System, New Haven, Connecticut, USA.
Elio Ragheb, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Jonathan Kluger, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Nitu Kashyap, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Carlos Paredes, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Prashant Patel, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Jing Lu, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Prakash Kandel, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Christopher Song, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Mustafa Khan, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Haocheng Huang, Yale School of Medicine, New Haven, Connecticut, USA.
Faheem Ul Haq, Yale New Haven Health System, New Haven, Connecticut, USA.
Rami Ahmad, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Christopher Howes, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Brian Cambi, Yale New Haven Health System, New Haven, Connecticut, USA.
Gilead Lancaster, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Michael Cleman, Yale New Haven Health System, New Haven, Connecticut, USA.Follow
Charles Dela Cruz, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Helen Parise, Yale School of Medicine, New Haven, Connecticut, USA.Follow
Alexandra Lansky, Yale School of Medicine, New Haven, Connecticut, USA alexandra.lansky@yale.edu.Follow

Document Type

Article

Publication Title

BMJ open

Abstract

OBJECTIVE: To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. DESIGN: A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up. SETTING: Four centres in the Yale New Haven Health System. PARTICIPANTS: Non-critically ill hospitalised patients with COVID-19. INTERVENTIONS: Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter. PRIMARY AND SECONDARY OUTCOME MEASURES: The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days. RESULTS: Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17). CONCLUSIONS: In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials. TRIAL REGISTRATION: NCT04472611.

First Page

e067910

DOI

10.1136/bmjopen-2022-067910

Publication Date

2-24-2023

Identifier

36828654 (pubmed); PMC9971831 (pmc); 10.1136/bmjopen-2022-067910 (doi); bmjopen-2022-067910 (pii)

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