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

Abstract

ObjectiveTo 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.DesignA 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.SettingFour centres in the Yale New Haven Health System.ParticipantsNon-critically ill hospitalised patients with COVID-19.InterventionsPatients 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 measuresThe 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.ResultsAmong 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).ConclusionsIn 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 registrationNCT04472611.

Prior Statin vs In-Hospital Statin Usage in Severe COVID-19: Review and Meta-Analysis

“…There were 8 randomized control studies in which the study arms included statins with anti-inflammatory and antiviral medications, which are listed in Table 2 . 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 Some of the studies had multiple treatment arms, and only the treatment arms with statins were compared to the control arm in these analyses. Main study outcomes of mortality and mechanical ventilation were analyzed between patients assigned to a treatment arm with statins and the control arm without statins.…”

Oxygen Saturation in Hospitalized COVID-19 Patients and Its Relation to Colchicine Treatment: A Retrospective Cohort Study with an Updated Systematic Review

“…Additionally, a randomized controlled trial (RCT) also supported our findings, which led to the early termination of the study. The use of a combination of colchicine and rosuvastatin was found to have a negative impact on non-critically hospitalized COVID-19 patients as it failed to prevent disease progression in multiple aspects, including the need for oxygen supplementation [ 56 ].…”

Statins in hospitalized COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

“…Of 2668 trials recognized by the initial search, 63 were retrieved for more detailed assessment, and 7 trials 7,8,[14][15][16][17][18] were included in this meta-analysis (Figure 1). Baseline characteristics of trials included in this meta-analysis are shown in Table 1.…”