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Studies

Interventional Recruiting Phase 3

NCT05855746 on ClinicalTrials.gov

Colchicine Versus Placebo in Acute Myocarditis Patients

Official title: Colchicine Versus Placebo in Acute Myocarditis Patients to Reduce Late Gadolinium Enhancement Mass on Cardiac Magnetic Resonance and the Risk of Clinical Outcomes: The ARGO Trial

  • Sponsor: Assistance Publique - Hôpitaux de Paris
  • Collaborators: Hospices Civils de Lyon, Fonds de Dotation ACTION
  • Enrollment: 300 (Estimated)
  • Study start: 2024-07-16 (Actual)
  • Primary completion: 2028-01-16 (Estimated)
  • Study completion: 2028-07-16 (Estimated)
  • Allocation: Randomized
  • InterventionModel: Parallel
  • InterventionModelDescription: 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.
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • PrimaryPurpose: Treatment

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

Intervention / Treatment

  • Drug: Colchicine Pill
  • Drug: Placebo

Primary Outcome Measures

  • Extent of Late Gadolinium Enhancement (LGE) evaluated on Cardiac Magnetic Resonance (CMR) (Six months post-randomization)
    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.
  • Composite Clinical primary outcome (Six months post-randomization)
    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

Countries

France

Locations and Investigators

  • Centre Hospitalier Saint Joseph Saint Luc, Lyon, France
    • Sylvain, RANC
  • Les Hopitaux De Chartres, Le Coudray, France
    • Christophe, THUAIRE
  • Institut Des Neurosciences De La Timone, Marseille, France
    • Florent, ARREGLE
  • Assistance Publique Hopitaux De Paris, Boulogne-Billancourt, France
    • Marie, HAUGUEL-MOREAU
  • Centre Hospitalier Universitaire D'Angers, Angers, France
    • Loic, BIERE
  • Assistance Publique Hopitaux De Paris, Paris Cedex 13, France
    • Florent, HUANG
  • Centre Hospitalier Groupe Hospitalier De La Rochelle Re Aunis, La Rochelle, France
    • Julien, LENESTOUR
  • Assistance Publique Hopitaux De Paris, Paris, France
    • Fabien, PICARD
  • Centre Hospitalier De Haguenau, Haguenau, France
    • Sabrina, UHRY
  • Centre Hospitalier Universitaire De Montpellier, Montpellier Cedex 5, France
  • Centre Hospitalier D Auxerre, Auxerre, France
    • Vincent, HUMEAU
  • Centre Hospitalier Annecy Genevois, Pringy Cedex, France
    • Victorien, MANNAZ
  • Union Mut Gestion Groupe Hosp Mutualiste De Grenoble, Grenoble, France
    • Benjamin, CASEZ
  • Centre Hospitalier Universitaire De Nimes, Nimes Cedex 9, France
  • Centre Hospitalier Regional Universitaire De Tours, Chambray Les Tours, France
    • Thibaud, GENET
  • Centre Hospitalier De Versailles, Le Chesnay Rocquencourt, France
    • Floriane, GILLES
  • Assistance Publique Hopitaux De Paris, Paris Cedex 10, France
  • Centre Hospitalier Universitaire De Nantes, Saint Herblain, France
    • Nicolas, PIRIOU
  • Hospices Civils De Lyon, Lyon Cedex 04, France
  • Centre Hospitalier Universitaire De Poitiers, Poitiers, France
    • Claire, BOULETI
  • Centre Hospitalier Metropole Savoie, Chambery, France
    • Thimothee, BESSEYRE DES HORTS
  • Centre Hospitalier Universitaire De Rennes, Rennes Cedex 9, France
    • Vincent, AUFFRET
  • Centre Hospitalier Universitaire De Nice, Nice, France
  • Hospices Civils De Lyon, Bron, France
    • Bertrand, SCHEPPLER
  • Centre Hospitalier Universitaire De Toulouse, Toulouse Cedex 9, France
    • Clément, DELMAS
  • Assistance Publique Hopitaux De Paris, Paris Cedex 18, France
    • Jérémie, ABTAN
  • Assistance Publique Hopitaux De Paris, Paris, France
  • Centre Hospitalier D Avignon, Avignon, France
    • Stéphane, ANDRIEU
  • Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace, Mulhouse, France
    • Didier, BRESSON

Study Officials