Beneficial effects of colchicine for moderate to severe COVID-19: an interim analysis of a randomized, double-blinded, placebo controlled clinical trial

Abstract

Introduction. Neutrophilia and high levels of proinflammatory cytokines and other mediators of inflammation are common finds in patients with severe acute respiratory syndrome due to COVID-19. By its action on leukocytes, we propose colchicine as an intervention worthy of being tested. Objective. To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes. Methods. We present the interim analysis of a single-center randomized, double-blinded, placebo controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 38 patients allocated 1:1 from April 11 to July 06, 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The first dose was 1.0 mg whether body weight was ≥ 80 kg. Endpoints. The primary endpoints were the need for supplemental oxygen; time of hospitalization; need for admission and length of stay in intensive care units; and death rate and causes of mortality. As secondary endpoints, we assessed: serum C-reactive protein, serum Lactate dehydrogenase and relation neutrophil to lymphocyte of peripheral blood samples from day zero to day 7; the number, type, and severity of adverse events; frequency of interruption of the study protocol due to adverse events; and frequency of QT interval above 450 ms. Results. Thirty-five patients (18 for Placebo and 17 for Colchicine) completed the study. Both groups were comparable in terms of demographic, clinical and laboratory data at baseline. Median (and interquartile range) time of need for supplemental oxygen was 3.0 (1.5-6.5) days for the Colchicine group and 7.0 (3.0-8.5) days for Placebo group (p = 0.02). Median (IQR) time of hospitalization was 6.0 (4.0-8.5) days for the Colchicine group and 8.5 (5.5-11.0) days for Placebo group (p = 0.03). At day 2, 53% vs 83% of patients maintained the need for supplemental oxygen, while at day 7 the values were 6% vs 39%, in the Colchicine and Placebo groups, respectively (log rank; p = 0.01). Hospitalization was maintained for 53% vs 78% of patients at day 5 and 6% vs 17% at day 10, for the Colchicine and Placebo groups, respectively (log rank; p = 0.01). One patient per group needed admission to ICU. No recruited patient died. At day 4, patients of Colchicine group presented significant reduction of serum C-reactive protein compared to baseline (p < 0.001). The majority of adverse events were mild and did not lead to patient withdrawal. Diarrhea was more frequent in the Colchicine group (p = 0.17). Cardiac adverse events were absent. Discussion. The use of colchicine reduced the length of supplemental oxygen therapy and the length of hospitalization. Clinical improvement was in parallel with a reduction on serum levels of C-reactive protein. The drug was safe and well tolerated. Colchicine may be considered a beneficial and not expensive option for COVID-19 treatment. Clinical trials with larger numbers of patients should be conducted to further evaluate the efficacy and safety of colchicine as an adjunctive therapy for hospitalized patients with moderate to severe COVID-19.

Anti-inflammatory therapy for COVID-19 infection: the case for colchicine

“…72 A third prospective study randomised 38 hospitalised COVID-19 patients to colchicine or placebo in a double-blinded manner. 73 Patients receiving colchicine had less need for supplemental oxygen at day 7 (6% vs 39%) and were more likely to be discharged at day 10 (94% vs 83%). Colchicine subjects also had greater reduction of CRP, and no increase in serious adverse events.…”

“…Colchicine subjects also had greater reduction of CRP, and no increase in serious adverse events. 73 Additional inpatient studies are ongoing (online supplemental table 2). Although the permitted use of other treatments could have biased the impact of colchicine in these studies, in the GRECO-19 trial no glucocorticoids were administered and other medications did not differ between the two groups; in the Italian study, there was no difference in outcomes among patients given colchicine who did or did not also receive dexamethasone.…”

Impact of colchicine on mortality in patients with COVID-19: A meta-analysis

“…A total of 112 articles were screened, 106 were excluded since they did not meet inclusion criteria ( Figure 1 ). A total of six studies, four published after peer-review 7 , 9 , 10 , 11 and two pre-prints 12 , 13 including 881 patients with confirmed COVID-19 were evaluated, 406 of whom were treated with colchicine in addition to standard-of-care ( Table ). To address one study 12 that reported no events in both arms, a value of 0.5 was added to the respective cells.…”

“…A total of six studies, four published after peer-review 7 , 9 , 10 , 11 and two pre-prints 12 , 13 including 881 patients with confirmed COVID-19 were evaluated, 406 of whom were treated with colchicine in addition to standard-of-care ( Table ). To address one study 12 that reported no events in both arms, a value of 0.5 was added to the respective cells. 14 The pooled odds ratio for mortality was 0.35 (95% confidence interval 0.24-0.52) and a similar significant trend was observed in terms of the risk difference ( Figure 2 A).…”

“… 11 USA 34/78 68/66 62/51 32/51 53/72 6/8 Pre-prints Lopes et al. 12 Brazil 17/18 48/54 53/28 29/33 ------ 47/33 § ------ Pinzón et al. 13 Colombia 145/156 NR NR NR NR NR Overall 406/475 CAD: Coronary Artery Disease, DM = Diabetes Mellitus, HTN= Hypertension, NR=Not Reported.…”