Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With COVID-19 (COLHEART-19)

Study Overview
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Brief Summary
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This is an open-label unblinded, randomized study to treat hospitalized covid-19 patients with colchicine plus current care (per institution treating physicians) vs. current care per institution treating physicians alone (the control arm)

Detailed Description
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We aim to determine if Colchicine improves short-term outcomes in hospitalized coronavirus disease-19 (COVID-19) patients with cardiac manifestations of disease. Myocardial injury has been described in up to 30% of COVID-19 infected patients, and portends a poor prognosis with currently no known treatment. Colchicine is a widely available, well-established, inexpensive, oral anti-inflammatory agent that has been FDA approved for the treatment of inflammatory disorders including gout and familial Mediterranean Fever. Trials have also shown its benefit to prevent post-cardiotomy syndrome, to treat acute and recurrent pericarditis, and reduce cardiovascular events after myocardial infarction. We extrapolate based on these indications and studies that colchicine may also help improve outcomes in hospitalized COVID-19 patients with evidence of cardiac injury. This is an unblinded randomized study to treat hospitalized covid-19 patients with colchicine plus current care per institution treating physicians vs. current care per institution treating physicians alone (the control arm)

Official Title
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Open-label (Unblinded) Randomization to Treatment of Colchicine Plus Current Care Per Institution Treating Physicians vs. Current Care Per Institution Treating Physicians (Control Arm)

Conditions
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Covid19

Intervention / Treatment
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* Drug: Colchicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women ≥ 18 years of age Covid-19 Positive Hospitalized patients able to provide informed consent Cardiac injury (as evidenced by any of the following) Elevated troponin level Elevated BNP level New ischemic or arrhythmogenic ECG/telemetry changes New decrease in Left Ventricular Ejection Fraction (LVEF) or new pericardial effusion on echocardiogram Exclusion Criteria: Pregnancy, breastfeeding mothers, and women of childbearing age who are unable to use adequate contraception, which includes: Intrauterine devices (IUD), contraceptive implants, or tubal sterilization Hormone method with a barrier method Two barrier methods If a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must also be used in conjunction History of severe hematologic or neuromuscular disorder Co-administration of Cytochrome P450 3A4 (CYPA3A4) and P-glycoprotein transport inhibitor Severe renal impairment with concomitant hepatic impairment Concurrent use of colchicine and strong or P-glycoprotein inhibitor with renal or hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an unblinded randomized study to treat hospitalized covid-19 patients with colchicine plus current care per institution treating physicians vs. current care per institution treating physicians alone (the control arm)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Hospitalized covid-19 patients treated with colchicine plus current care per institution treating physicians. | Drug: Colchicine<br>* Colchicine dosing = 0.6 mg bid x 30 days Decrease dose to 0.3-0.6 mg daily or every other day in setting of gastrointestinal intolerance (nausea, diarrhea, emesis, abdominal discomfort) Decrease dose to 0.6 mg daily in the setting of weak or moderate CYP3A4 inhibitor Decrease dose to 0.3 mg daily in the setting of strong CYP3A4, P-glycoprotein inhibitors, or protease inhibitors Decrease dose to 0.3 mg daily in the setting of chronic kidney disease (CKD) stage ≥ 4 (CrCl ≤ 30 ml/min) or liver failure (aspartate aminotransferase /alanine aminotransferase > 3x normal). Decrease dose to 0.6 mg every 14 days in patients with end stage renal disease (ESRD) or requiring dialysis Route of Administration: oral<br>* Other names: Treatment with Colchicine plus standard of care in hospitalized patients with Covid-19;|
| No Intervention: Control<br>Hospitalized covid-19 patients treated with current standard of care (per institution treating physicians) alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Composite of all-cause mortality | 90 days | 
| Mechanical Ventilation | Need for mechanical ventilation | 90 days | 
| Mechanical Circulatory Support | Need for mechanical circulatory support | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (Days) to the Primary End Point | Number of days from start of therapy to either mortality or need for Mechanical Ventilation or Mechanical Circulatory Support | 90 days | 
| Peak and Delta (Change From Baseline) Troponin Level | Change from baseline to the time when Troponin levels peak during the hospitalization | baseline and 90 days | 
| Baseline Brain Natriuretic Peptide (BNP) Level | Documenting baseline Brain Natriuretic Peptide (BNP) at the time of hospitalization | baseline | 
| Inflammatory Biomarkers | Baseline and delta (change from baseline) of C-Reactive Protein | baseline and 90 days | 
| Hospital Length of Stay | Duration of Hospitalization on each arm | 90 days | 
| Need for Re-hospitalization | 90-day re-hospitalization rate | 90 days | 
| Change in Inflammatory Biomarkers | Baseline and delta (change from baseline) of D-Dimer | baseline and 90 days |