Colchicine Versus Placebo in Acute Myocarditis Patients

NCT ID: NCT05855746

Last Updated: 2025-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-16

Study Completion Date

2028-07-16

Brief Summary

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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.

Detailed Description

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This study is a prospective, randomized, multicenter, double blind, controlled versus placebo, phase III study in which two groups of participants are compared: a group treated with the experimental treatment Colchicine (in addition to standard of care therapy) compared to a control group that receive the corresponding placebo (in addition to standard of care therapy).

The inclusion visit takes place during the initial hospitalization stay. The study is presented to all patients presenting with acute myocarditis symptoms and inclusion criteria, hospitalized in participating centers.

Once eligible participants have been informed and signed their informed consent, they are randomized (1:1) by a centralized web system (IWRS) in the experimental group (Colchicine) or the control group (Placebo).

Participants receive then a numbered box with three months' treatment of Colchicine or placebo. The treatment must start at least within 72h after randomization. Another dispensing is performed during the three months' follow-up visit.

All randomized participants are followed during six months after the end of the treatment.

Conditions

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Acute Myocarditis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Colchicine

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

Group Type EXPERIMENTAL

Colchicine Pill

Intervention Type 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.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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Colchicine Pill

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Other Intervention Names

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Colchicine

Eligibility Criteria

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Inclusion Criteria

* Symptom onset of 21 days or less,
* Chest pain and/or Heart failure symptoms and/or palpitations
* Troponins superior to 99 percentile of reference value,
* 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.

Exclusion Criteria

* 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, non-MR compatible cardiac devices (pace maker or defibrillator); history of hypersensitivity to gadoteric acid or to gadolinium contrast agents or to meglumine),
* Chronic treatment with corticosteroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 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),
* Cytopenia : hemoglobin less than 100 grams/L, white blood cell count less than 3.0 G/L, platelet count less than 100 G/L
* Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
* Immunosuppression, spinal cord aplasia
* Hemopathy
* Hypereosinophilia more than 0.5 G/L
* 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,
* Administration of any investigational drug or participation in another interventional trial, within 30 days before randomization,
* Participant under treatment having an interaction with colchicine \[macrolides (telithromycin, azithromycin, clarithromycin, dirithromycin, erythromycin, josamycin, midecamycin, roxithromycin), pristinamycin,, cyclosporine, verapamil, all protease inhibitors, telaprevir, CYP3A4 powerful inhibitors, azole antifungals, vitamin K antagonists\]
* Participant under legal protection: under guardianship (trusteeship or curatorship)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role collaborator

Fonds de Dotation ACTION

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas BOCHATON

Role: STUDY_CHAIR

Cardiovascular hospital Louis Pradel

Mathieu KERNEIS

Role: STUDY_DIRECTOR

Department of Cardiology - Pitié Salpêtrière Hospital

Locations

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Unité de Soins Intensifs Cardiologiques - Hôpital Cardiovasculaire Louis Pradel

Bron, , France

Site Status RECRUITING

Institut de Cardiologie - APHP Pitié Salpêtrière

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Thomas BOCHATON

Role: CONTACT

+33472357549

Julia CANTERINI

Role: CONTACT

+33427856628

Facility Contacts

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Thomas BOCHATON

Role: primary

+33472357549

Julia CANTERINI

Role: backup

+33427856628

Mathieu KERNEIS

Role: primary

+33142163074

Karine BROCHARD

Role: backup

+3142162959

References

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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.

Reference Type BACKGROUND
PMID: 31120823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29764898 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25468248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32138965 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23992557 (View on PubMed)

Other Identifiers

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APHP211429

Identifier Type: -

Identifier Source: org_study_id

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