Colchicine Versus Placebo in Acute Myocarditis Patients

NCT05855746 | Recruiting Phase 3 DMC

• 1 other identifier: APHP211429
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

Myocarditis is an inflammatory disease of the heart, mostly caused by viruses. Patients with acute myocarditis are exposed to several complications: recurrence, ventricular arrhythmias (from 5 to 30%), heart failure (5-10%), death or heart transplantation (\< 4%). To date, there is no specific treatment for myocarditis. Patient management only focuses upon empirical optimal care of arrhythmia and heart failure. There is a strong rationale for using colchicine in acute myocarditis:

• the IL1 (Interleukin1) pathway plays a detrimental role in acute myocarditis. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome assembly, and subsequent IL-1beta production, are profoundly inhibited by colchicine.
• colchicine has been shown to improve cardiac outcomes in inflammatory cardiac disorders, including pericarditis, coronary artery disease, and post pericardiotomy syndrome.
• In murine model of CVB3-induced myocarditis (coxsackievirus B3), colchicine improved myocarditis through reduction of NLRP3 activity.
• Small case series with improvement of left ejection fraction in myocarditis following low-dose colchicine in addition to conventional heart failure therapy have been reported. With its pleiotropic anti-inflammatory effect in the pro-inflammatory cascade, reducing the myocardial damage and cell death induced during myocarditis, colchicine has the potential to reduce the risk of heart failure and ventricular arrhythmias. Finally, colchicine is a drug widely available, at low cost, and has a long and well-known safety record.

Conditions

Acute Myocarditis

Keywords

Myocarditis; Inflammation; Colchicine

Outcome Measures

Primary Outcomes (2)

• Extent of Late Gadolinium Enhancement (LGE) evaluated on Cardiac Magnetic Resonance (CMR)

  Extent of LGE (pourcentage of left ventricle mass) is evaluated (centralized reading by the Corelab) on CMR performed at six months and compared to baseline CMR (performed at the hospital admision or inclusion). The inclusion visit takes place during the initial hospitalization.

  Six months post-randomization

• Composite Clinical primary outcome

  Composite Clinical primary outcome is assessed during the study period at six months on: * the rate of heart Failure or acute myocarditis recurrence; * or the rate of clinically relevant chest pain (defined as leading to an unplanned/urgent consultation or hospitalization or requiring an additional treatment); * or the rate of sustained ventricular arrhythmias; * or the rate of left ventricular assistance; * or the rate of heart transplantation; * or the rate of cardiovascular death

  Six months post-randomization

Secondary Outcomes (23)

• Safety of colchicine

  Six months post-randomization

• Composite clinical secondary outcome

  one year post-randomization

• Rate of heart failure at 6 months

  Six months post-randomization

• Rate of acute myocarditis recurrence at 6 months

  Six months post-randomization

• Rate of clinically relevant chest pain at 6 months

  Six months post-randomization

Study Arms (2)

Colchicine

EXPERIMENTAL

Participant receive in addition to standard of care therapy, six months of Colchicine

Drug: Colchicine Pill

Placebo

PLACEBO COMPARATOR

Participant receive in addition to standard of care therapy, six months of placebo

Drug: Placebo

Interventions

Colchicine Pill DRUG

Participant receive, in addition to standard of care therapy, six months of colchicine (at a dose of 0.5 mg twice daily, morning and evening) beginning maximum 72 hours post-randomization. The standard of care is defined according to the European consensus paper as follow: All participants without contraindication receive a betablockers, and heart failure ESC (European Society of Cardiology) guidelines directed medical therapies if LVEF \< 50% (Left Ventricular Ejection Fraction), including ACE (Angiotensin-Converting Enzyme) inhibitors, diuretics if indicated. The choice of the dosage and the drug is left at the investigator decision. During the six months of the treatment administration, in case of severe adverse reaction (such as nausea and/or diarrhea during five days), a dose reduction could be considered by the investigator: half of the study protocol dose could be accepted (0.5 mg per day in the morning). In case of remaining adverse reactions, the study drug should be stopped.

Also known as: Colchicine

Colchicine

Placebo DRUG

Participant receive, in addition to standard of care therapy, six months of placebo (at a dose of 0.5 mg twice daily, morning and evening) beginning maximum 72 hours post-randomization. The standard of care is defined according to the European consensus paper as follow: All participants without contraindication receive a betablockers, and heart failure ESC (European Society of Cardiology) guidelines directed medical therapies if LVEF \< 50% (Left Ventricular Ejection Fraction), including ACE (Angiotensin-Converting Enzyme) inhibitors, diuretics if indicated. The choice of the dosage and the drug is left at the investigator decision.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptom onset of 28 days or less,
• Myocarditis initially presenting with chest pain and/or Heart failure symptoms and/or palpitations
• Myocarditis diagnostic confirmation (by Contrast-Enhanced Cardiac Magnetic Resonance (CMR), according to the Lake Louise criteria (2009 or later),
• No evidence for ischemic heart disease on coronary angiography or coronary computed tomography angiography for patients with age superior to 40-year-old with one or more cardiovascular risk factor (hypertension, smoking, hypercholesterolemia, diabetes, personal or family history of coronary artery disease),
• Woman of child-bearing age with an effective contraception method according to the investigator for the duration of treatment and one month after,
• Man accepting effective contraception for the duration of treatment and one month after,
• Participant with affiliation to the French Health Care System "sécurité sociale",
• Written informed consent of the patient obtained.

You may not qualify if:

• Cardiogenic shock requiring inotropes or vasopressors (patients with inotropes discontinued for more than 24 hours can be enrolled)
• Giant cell myocarditis or eosinophilic myocarditis
• Acute coronary syndrome or known coronary stenosis superior to 50%
• Toxic cardiomyopathy
• Active chronic inflammatory disease, chronic active infection, evolving cancer
• A recent severe sepsis (7 days)
• Hypersensitivity to Investgational Medical Product's active substances (colchicine) or to any of the excipients (including lactose, sucrose, microcrystalline cellulose, colloidal silica, magnesium stearate, colourants : E127, Dual Red 40 )
• Any known contra-indication to CMR or associated contract products (claustrophobia; intra-ocular metal foreign bodies, clips such as cerebral, carotid, or aortic aneurysm, cochlear implants, any implant held in by magnet, history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine). Patients with an implantable cardioverter-defibrillator (ICD) or pacemaker (PM) are also excluded due to the risk of imaging artifacts, which may compromise the reliable quantification of late gadolinium enhancement (LGE).
• Chronic treatment with corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or high-dose aspirin or immunosuppressant.
• Sarcoidosis
• Severe liver (Child Pugh C) or known renal dysfunction (known Glomerular Filtration Rate (GFR) less or equal to 30 ml/min according Cockroft),
• Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
• Immunosuppression, spinal cord aplasia
• Hemopathy
• Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive local laboratory test,

Sponsors & Collaborators

• Hospices Civils de Lyon: collaborator
• Fonds de Dotation ACTION: collaborator
• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Unité de Soins Intensifs Cardiologiques - Hôpital Cardiovasculaire Louis Pradel

Bron, 69029, France

RECRUITING

Institut de Cardiologie - APHP Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Related Publications (5)

• Tschope C, Cooper LT, Torre-Amione G, Van Linthout S. Management of Myocarditis-Related Cardiomyopathy in Adults. Circ Res. 2019 May 24;124(11):1568-1583. doi: 10.1161/CIRCRESAHA.118.313578.

  PMID: 31120823 BACKGROUND

• Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Ciro A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11;138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319.

  PMID: 29764898 BACKGROUND

• Kyto V, Sipila J, Rautava P. Rate and patient features associated with recurrence of acute myocarditis. Eur J Intern Med. 2014 Dec;25(10):946-50. doi: 10.1016/j.ejim.2014.11.001. Epub 2014 Nov 7.

  PMID: 25468248 BACKGROUND

• Peretto G, Sala S, Rizzo S, Palmisano A, Esposito A, De Cobelli F, Campochiaro C, De Luca G, Foppoli L, Dagna L, Thiene G, Basso C, Della Bella P. Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation. J Am Coll Cardiol. 2020 Mar 10;75(9):1046-1057. doi: 10.1016/j.jacc.2020.01.036.

  PMID: 32138965 BACKGROUND

• Imazio M, Brucato A, Cemin R, Ferrua S, Maggiolini S, Beqaraj F, Demarie D, Forno D, Ferro S, Maestroni S, Belli R, Trinchero R, Spodick DH, Adler Y; ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013 Oct 17;369(16):1522-8. doi: 10.1056/NEJMoa1208536. Epub 2013 Aug 31.

  PMID: 23992557 BACKGROUND

MeSH Terms

Conditions

Myocarditis; Inflammation

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Thomas BOCHATON

  Cardiovascular hospital Louis Pradel

  STUDY CHAIR

• Mathieu KERNEIS

  Department of Cardiology - Pitié Salpêtrière Hospital

  STUDY DIRECTOR

Central Study Contacts

Thomas BOCHATON

CONTACT

+33472357549; thomas.bochaton@chu-lyon.fr

Julia CANTERINI

CONTACT

+33427856628; julia.canterini@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, two arms, randomized (1:1), double blind, superiority study evaluating colchicine versus placebo administrated during six months among participants with acute myocarditis.

Study Record Dates

• First Submitted: April 21, 2023
• First Posted: May 11, 2023
• Study Start: July 16, 2024
• Primary Completion (Estimated): January 16, 2028
• Study Completion (Estimated): July 16, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)