Background Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.Methods The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0•5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97•9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FindingsTrial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53•9% women; median age 54•0 years, IQR 47•0-61•0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4•7%) of 2235 patients in the colchicine group and 131 (5•8%) of 2253 patients in the placebo group (odds ratio [OR] 0•79, 95•1% CI 0•61-1•03; p=0•081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4•6%) of 2075 patients in the colchicine group and 126 (6•0%) of 2084 patients in the placebo group (OR 0•75, 0•57-0•99; p=0•042). Serious adverse events were reported in 108 (4•9%) of 2195 patients in the colchicine group and 139 (6•3%) of 2217 patients in the placebo group (p=0•051); pneumonia occurred in 63 (2•9%) of 2195 patients in the colchicine group and 92 (4•1%) of 2217 patients in the placebo group (p=0•021). Diarrhoea was reported in 300 (13•7%) of 2195 patients in the colchicine group and 161 (7•3%) of 2217 patients in the placebo group (p<0•0001).Interpretation In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to pr...

Background Acute kidney injury ( AKI ) after cardiac surgery is associated with adverse outcomes. Venous congestion can impair kidney function, but few tools are available to assess its impact at the bedside. The objective of this study was to determine whether portal flow pulsatility and alterations in intrarenal venous flow assessed by Point‐Of‐Care ultrasound are associated with AKI after cardiac surgery. Methods and Results This single‐center prospective cohort study recruited patients undergoing cardiac surgery with cardiopulmonary bypass. Hepatic and renal Doppler ultrasound assessments were performed before surgery, at the intensive care unit admission, and daily for 3 days after surgery. The primary statistical analysis was performed using proportional hazards model for time‐dependent variables. Among the 145 patients included, 49 patients (33.8%) developed AKI after cardiac surgery. The detection of portal flow pulsatility was associated with an increased risk of AKI (hazard ratio: 2.09, confidence interval, 1.11–3.94, P=0.02), as were severe alterations of intrarenal venous flow (hazard ratio: 2.81, confidence interval, 1.42–5.56, P =0.003). These associations remained significant in multivariable models. The addition of these markers to preoperative risk factors and central venous pressure measurement at intensive care unit admission improved the prediction of AKI . (Continuous net reclassification improvement: 0.364, confidence interval, 0.081–0.652 for portal Doppler and net reclassification improvement: 0.343, confidence interval, 0.081–0.628 for intrarenal Doppler) Conclusions Portal flow pulsatility and intrarenal flow alterations are markers of venous congestion and are independently associated with AKI after cardiac surgery. These tools might offer valuable information to develop strategies aimed at treating or preventing congestive cardiorenal syndrome after cardiac surgery. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02831907.

Aims The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. Methods and results In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (&lt;3, 4–7 and &gt;8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated &lt; Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or &gt; Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P &lt; 0.05). Conclusion Patients benefit from early, in-hospital initiation of colchicine after MI. Trial Registration COLCOT ClinicalTrials.gov number, NCT02551094.

BackgroundEvidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.MethodsWe performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.ResultsA total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).ConclusionAmong non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

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Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure. Only half of the patients recover normal cardiac function. We assessed the usefulness of magnetic resonance imaging (MRI) and late enhancement imaging to detect myocardial fibrosis in order to predict cardiac function recovery in patients with peripartum cardiomyopathy. Among a consecutive series of 1,037 patients referred for heart failure treatment or prognostic evaluation between 1999 and 2006, eight women had confirmed PPCM. They all underwent echocardiography and cardiac MRI for assessment of left ventricular anatomy, systolic function and detection of myocardial fibrosis through late enhancement imaging. Mean (+/- SD) baseline left ventricular ejection fraction (LVEF) was 28 +/- 4%. After a follow-up of 50 +/- 9 months, half the patients recovered normal cardiac function (LVEF = 58 +/- 4%) and four did not (LVEF = 35 +/- 6%). None of the eight patients exhibited abnormal myocardial late enhancement. No difference in MRI characteristics was observed between the two groups. Patients with PPCM do not exhibit a specific cardiac MRI pattern and particularly no myocardial late enhancement. It suggests that myocardial fibrosis does not play a major role in the limitation of cardiac function recovery after PPCM.

ClinicalTrials.gov Identifier NCT01035255.

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