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

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

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)

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Colchicine

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

  1. Elevated troponin level
  2. Elevated BNP level
  3. New ischemic or arrhythmogenic ECG/telemetry changes
  4. 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:

  1. Intrauterine devices (IUD), contraceptive implants, or tubal sterilization
  2. Hormone method with a barrier method
  3. Two barrier methods
  4. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active; Hospitalized covid-19 patients treated with colchicine plus current care per institution treating physicians.	Drug: Colchicine; 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; Other Names: Treatment with Colchicine plus standard of care in hospitalized patients with Covid-19
No Intervention: Control; Hospitalized covid-19 patients treated with current standard of care (per institution treating physicians) alone.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baptist Health South Florida
• Collaborators: University of California, Los Angeles

Publications and helpful links

General Publications

• Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2020
• Primary Completion (Actual): May 12, 2021
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 152247

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No