Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial
Tayyab Shah, Marianne Mccarthy, Irem Nasir, Herb Archer, Elio Ragheb, Jonathan Kluger, Nitu Kashyap, Carlos Paredes, Prashant Patel, Jing Lu, Prakash Kandel, Christopher Song, Mustafa Khan, Haocheng Huang, Faheem Ul Haq, Rami Ahmad, Christopher Howes, Brian Cambi, Gilead Lancaster, Michael Cleman, Charles Dela Cruz, Helen Parise, Dr Alexandra Lansky
BMJ Open, doi:10.1136/bmjopen-2022-067910
Objective To evaluate the effect of colchicine and highintensity 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.
Ethics approval This study involved human participants and was approved by Yale Institutional Review Board (IRB Protocol ID: 2000027950). Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The data contains protected patient information and at this time are not available to be shared publicly. *This analysis excluded all patients in active arm who did not receive both colchicine and rosuvastatin for at least 1 dose in hospital and all patients in standard of care arm who received a single dose of colchicine or any statin in hospital. BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)
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