Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

Importance: Hospitalized 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 Measures: The 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%). Conclusions and Relevance: This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04328480.

Development and validation of a predictive model of in-hospital mortality in COVID-19 patients.

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.