July 29, 2020
Reviewed by Erica Kaufman West, M.D.
There appears to be two phases of COVID-19, an early viremic phase and a later inflammatory phase, which can cause severe disease and hospitalization. Many researchers are looking at medications – novel and repurposed – to combat this inflammatory response. In a recent JAMA Network Open article, the authors looked at colchicine, due to its various anti-inflammatory properties.
As infections in Greece slowed, the study enrolled 105 patients, short of the 180 needed to power the study to its primary clinical end point, defined as time from baseline to clinical deterioration (a 2-grade increase on the World Health Organization [WHO] Ordinal Clinical Scale). The primary biochemical end point was maximal high-sensitivity cardiac troponin levels and time for C-reactive protein (CRP) to reach levels greater than three times the upper reference limit. Secondary end points were the percent of patients requiring mechanical ventilation, all-cause mortality at the end of follow-up, and side-effect data. Unlike many COVID-19 studies, this was a prospective, open-label, randomized clinical trial, which is to be applauded.
Colchicine and control groups were similar in presentation and baseline labs and demographics; 98% of patients got chloroquine or hydroxychloroquine. Days of hospitalization were not different between the two groups, interestingly. Baseline WHO clinical score was 4 in both groups (i.e., hospitalized requiring supplemental oxygen) and seven patients in the control arm and one in the colchicine group had a ≥ 2 grade increase (a score of 6 is ECMO and/or invasive mechanical ventilation, and 7 is death) with a P = 0.02. Cumulative event-free 10-day survival was 83% in the control and 97% in the colchicine groups. Not surprisingly, diarrhea was more common in the colchicine arm, with two of 55 patients stopping due to that side effect. Biomarkers remained similar except for d-dimer, which was lower in the colchicine arm by a statistically significant amount, although that laboratory value was not a predefined end point. Troponin and CRP, which were predefined, were not different.
Given the small number of clinical events (seven vs. one) and because it did not meet its enrollment goal, the authors appropriately note that this study should be hypothesis generating and encourage others to pick up where it left off with additional randomized trials. Colchicine is already available and production could be ramped up if these initial findings are replicated on a larger scale.