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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Colchicine Tablets; Other: Current care per UCLA treating physicians

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Ronald Reagan Medical Center
    • Santa Monica, California, United States, 90404
      • UCLA Santa Monica Hospital
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cardiac and Vascular Institutde, Baptist Health South Florida

Participation Criteria

Eligibility Criteria

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

Description

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

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
Experimental: Colchicine plus current care; Colchicine 0.6 mg po BID x 30 days plus current care per UCLA treating physicians	Drug: Colchicine Tablets; 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.; Other Names: COLCRYS; AR 374; Other: Current care per UCLA treating physicians; Current care
Active Comparator: Current care alone; Current care per UCLA physicians alone (control arm)	Other: Current care per UCLA treating physicians; Current care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Reza Ardehali, MD, PhD, University of California, Los Angeles

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Rabbani A, Rafique A, Wang X, Campbell D, Wang D, Brownell N, Capdevilla K, Garabedian V, Chaparro S, Herrera R, Parikh RV, Ardehali R. Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With Coronavirus Disease-19. Front Cardiovasc Med. 2022 Jun 17;9:876718. doi: 10.3389/fcvm.2022.876718. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): July 21, 2021
• Study Completion (Actual): July 21, 2021

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 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: 20-000685

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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