Table 1.

Randomized clinical trials that investigated colchicine in patients with COVID-19

Authors	Design	Study population	Colchicine dose	Main findings
Hospitalized patients
Deftereos et al. GRECCO-19 Randomized Clinical Trial [23]	Prospective, open-label, RCT	50 hospitalized patients in the SOC group  55 hospitalized patients in the SOC + colchicine group	Loading dose: 1.5 mg followed by 0.5 mg of colchicine after 1 h (loading dose 1 mg in case of azithromycin co-administration)  Maintenance: dosage: 0.5 mg twice daily (once daily if body weight < 60 kg) until hospital discharge or a maximum of 21 days	The primary clinical endpoint (time from baseline to clinical deterioration based on WHO ordinal clinical scale) occurred more frequently in the SOC vs. colchicine group (14% vs. 1.8%; OR 0.11, 95% CI 0.01–0.96. p = 0.046) Event-free 10-day survival was 83% vs. 97% in the control vs. interventional group (p = 0.03) Similar AEs were observed in the 2 groups, except for diarrhea that was more frequent in the colchicine arm (45.5% vs. 18.0%, p = 0.003)
Lopes et al. [26]	Double-blind, placebo-controlled RCT	37 hospitalized patients in the placebo group  37 hospitalized patients in the colchicine group	0.5 mg three times daily for 5 days, then 0.5 mg twice daily for 5 days  If weight ≥ 80 kg, first dose was 1.0 mg  If eGFR < 30 mL/min/1.73 m2, 0.25 mg three times daily for 5 days, then 0.25 mg twice daily for 5 days	Patients treated with colchicine stopped using supplemental oxygen before those in the placebo group (median 4 vs. 6.5 days, p < 0.001) and had a reduced length of hospital stay (median 7 vs. 9 days, p = 0.003) Across 1 week, patients treated with colchicine experienced a marked reduction in CRP levels compared with those in the placebo group (p < 0.001) Common AEs like diarrhea and pneumonia were more frequent in the colchicine and placebo groups, respectively
RECOVERY Collaborative Group RECOVERY Trial [31]	Investigator-initiated, open-label RCT	5730 hospitalized patients in the SOC group (dexamethasone, HCQ, lopinavir/ritonavir, azithromycin, tocilizumab, and convalescent plasma)  5610 hospitalized patients in the colchicine group	1 mg after randomization, then 0.5 mg 12 h later, followed by 0.5 mg twice daily for 10 days or until discharge, whichever came first, or 0.5 mg once daily for patients receiving a moderate CYP3A4 inhibitor or with eGFR < 30 mL/min/1.73 m2 or estimated body weight < 70 kg	No difference in the proportion of patients meeting the primary outcome (all-cause mortality) was found (1173 patients in the colchicine group vs. 1190 patients in the SOC group; RR 1.01, 95% CI 0.93–1.10, p = 0.77) No secondary outcome (time to discharge, need for MV, or death) was met Two AEs probably related to colchicine were recorded (AKI and rhabdomyolysis)
Mareev et al. COLORIT study [86]	Prospective, comparative, quasi-randomized trial	22 hospitalized patients in the control group (no anti-inflammatory therapy)  21 hospitalized patients in the colchicine group	1 mg daily up to day 3, then 0.5 mg daily up to 14 days	The primary endpoint (SHOCS-COVID score reduction after treatment) was met by the colchicine group (8 vs. 2, p = 0.017), but not by control group
Pascual-Figal et al. [87]	Prospective, randomized, controlled, open-label RCT	51 hospitalized patients without MV receiving standard treatment  52 patients without MV receiving colchicine on top of standard treatment	Loading dose of 1.5 mg (1 mg followed by 0.5 mg 2 h later), then 0.5 mg twice daily for the next 7 days, and then 0.5 mg once daily until day 28	Colchicine was associated with a lower risk of clinical deterioration (OR 0.11, p = 0.03) At day 28, all patients treated with colchicine were discharged alive, while 2 patients died in the standard treatment arm and one was still hospitalized
Outpatients
Tardif et al. ColCORONA Trial [30]	Randomized, double-blind, placebo-controlled, investigator-initiated RCT	2253 non-hospitalized patients in the placebo group  2235 non-hospitalized patients in the colchicine group	Colchicine: 0.5 mg twice daily for the first 3 days, then once daily for 27 days	No difference in the occurrence of the primary endpoint (a composite of death or hospitalization within 30 days from randomization) was observed between groups Among those with a PCR-confirmed COVID-19 diagnosis, the primary endpoint occurred less frequently in colchicine-treated patients vs. placebo (OR 0.75, 95% CI 0.57–0.99, p = 0.04). The risk for hospitalization was decreased (OR 0.75, 95% CI 0.57–0.99), but no effect on death was seen Serious AEs were 4.9% in the colchicine group and 6.3% in the placebo, with pneumonia occurring less frequent and diarrhea more frequent in the colchicine arm

Where available, SOC therapy was included

AE adverse event. AKI acute kidney injury. CI confidence interval. COVID-19 coronavirus disease 2019. CRP C-reactive protein. CYP3A4 cytochrome P450 3A4. eGFR estimated glomerular filtration rate. MV mechanical ventilation. OR odds ratio. PCR polymerase chain reaction. RCT randomized clinical trial. RR rate ratio. SHOCS-COVID Symptomatic Hospital and Outpatient Clinical Scale for COVID-19. SOC standard-of-care. WHO World Health Organization