Colchicine to Reduce Cardiac Injury in COVID-19 (COLHEART-19)

Study Overview
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Brief Summary
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Participants will be randomized in a 1:1 ratio to receive Colchicine plus current care per UCLA treating physicians versus current care per UCLA treating physicians alone (control arm). Importantly, this adaptive trial design allows for patients in either study arm to receive other investigational drugs for COVID-19 as new science emerges.

Official Title
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Randomized, Open-Label, Controlled Trial of Colchicine to Reduce Cardiac Injury in Hospitalized COVID-19 (Coronavirus Disease 2019) Patients (COLHEART-19)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Colchicine Tablets
* Other: Current care per UCLA treating physicians


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed COVID-19 infection by polymerase chain reaction Cardiac injury, including any of the following: Elevated troponin level Elevated B-type natriuretic peptide (BNP) level New ischemic or arrhythmogenic changes on ECG/telemetry New decrease in left ventricular ejection fraction (LVEF) or new pericardial effusion on echocardiogram Able to provide informed consent Exclusion Criteria: Pregnancy, breastfeeding mothers, and women of childbearing age who are unable to use 2 forms of contraception, which includes: Intrauterine devices (IUD), contraceptive implants, or tubal sterilization Hormone methods 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 Co-administration of Cytochrome P450 3A4 (CYPA3A4) and P-glycoprotein (P-gp) transport system inhibitors Concurrent use of strong CYP3A4 or P-gp inhibitors in patients with renal or hepatic impairment; Severe hematologic or neuromuscular disorders Severe renal impairment with concomitant hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 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: Random assignment to study arms in a 1:1 ratio
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine plus current care<br>Colchicine 0.6 mg po BID x 30 days plus current care per UCLA treating physicians | Drug: Colchicine Tablets<br>* COLCRYS (colchicine, USP) tablets for oral administration, containing 0.6 mg of the active ingredient colchicine USP, administered po every 12 hours x 30 days.<br>* Other names: AR 374;Other: Current care per UCLA treating physicians<br>* Current care<br>|
| Active Comparator: Current care alone<br>Current care per UCLA physicians alone (control arm) | Other: Current care per UCLA treating physicians<br>* Current care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of All-cause Mortality, Need for Mechanical Ventilation, or Need for Mechanical Circulatory Support (MCS) | Number of participants experiencing any of the following: All-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS) | 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta (Peak Minus Baseline) Troponin Level | Change from initial troponin level to maximum level of troponin among measures taken during hospitalization and at 30 days | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | 
| Delta (Baseline to Peak) Brain Natriuretic Peptide (BNP) Level | Change from baseline BNP level (Day 1) to maximum level of BNP among measures taken during hospitalization and at 30 days | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | 
| Change in Left Ventricular Ejection Fraction (LVEF) on Echocardiography | Number of participants experiencing LVEF of < 50% on echocardiogram with failure to show an improvement of ≥ 5% at 30 days | Baseline, Day 30 | 
| Delta (Peak Minus Baseline) C-Reactive Protein (CRP) Inflammatory Biomarker Level | Change from baseline CRP level (Day 1) to maximum level of CRP among measures taken during hospitalization and at 30 days | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | 
| Delta (Peak Minus Baseline) D-Dimer Inflammatory Biomarker Level | Change from baseline D-Dimer level (Day 1) to maximum level among measures taken during hospitalization and at 30 days. D-Dimer is a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis, so named because it contains two D fragments of the fibrin protein joined by a cross-link. | Baseline (Day 1), Day 30, Days 3 and 7 if hospitalized | 
| Composite Event-Free Survival Over Time (Days) | Participants reaching primary (composite) endpoint were subtracted from event-free survival reported at 10-day intervals | Days 0, 10, 20, 30, 40, 50, 60, 70, 80, and 90 | 
| Number of Participants Requiring Mechanical Ventilation |  | 90 days | 
| Number of Participants Requiring Mechanical Circulatory Support (MCS) |  | 90 days | 
| Re-hospitalization at 90 Days | Number of participants released and re-admitted to the hospital within 90 days of enrollment | 90 days | 
| All-cause Mortality |  | 90 days |