Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19

Abstract

IMPORTANCEHospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. OBJECTIVE To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. INTERVENTIONS Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine.Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. MAIN OUTCOMES AND MEASURESThe first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. RESULTS A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%)in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%).

Effect of colchicine on mortality in patients with COVID-19 – A systematic review and meta-analysis

“…There were 12 studies comprising of 6953 patients included in this meta-analysis [ 10 , 11 , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] ] [ Fig. 1 ].…”

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial

“…On the other hand, the colchicine arm of the RECOVERY trial, a large randomized clinical trial, found no clinical benefit. Moreover, colchicine showed no beneficial effect on the need of mechanical ventilation or 28-day mortality in a recent randomized clinical trial including 1279 patients hospitalized with COVID-19 pneumonia 21 . Nevertheless, none of these previous studies focused on patients with COVID-19 pneumonia and established hyperinflammation, a subset of patients particularly attractive to assess the effect of colchicine.…”

“…Interestingly, in the scenario of SARS-CoV-2 infection, overweight and obesity are associated with a higher risk of hospital admission 22 and progression to severe COVID 23 . However, since the RECOVERY and ECLA PHRI COLCOVID trials did not collect BMI information 12 , 21 , this is the first clinical trial analyzing the effect of colchicine on overweight patients. Remarkably, the excess of macronutrients in the adipose tissues predisposes to the releases of inflammatory mediators which participate in the cytokine storm aggravating COVID-19 2 .…”

Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

“…A randomized, controlled phase II/III trial in hospitalized COVID-19 patients indicated that colchicine could not reduce mechanical ventilation requirement, length of hospital stay, and 28-day mortality (NCT04381936), 165 in line with results of another clinical trial (NCT04328480). 166 Thus, the efficacies of colchicine by the single or combined treatment should be further studied.…”