2024-510602-90-00RecruitingPhase 3
COTAM - Use of glucocorticoids therapy in acute myocarditis with severe left ventricular dysfunction: a multicenter randomized controlled trial
Assistance Publique Hopitaux De Paris22 sites in 1 country420 target enrollmentStarted: March 20, 2025Last updated:
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 420
- Locations
- 22
- Primary Endpoint
- Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF < 50% and/or Global Longitudinal Strain (GLS) < - 16% between baseline (D-2) and 6 months (M6) follow up. MACE is a combined criterion that includes all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or assistance and recurrent acute myocarditis with LV dysfunction at 6 months
Study Overview
Brief Summary
To evaluate in patients with acute myocarditis and left-ventricular dysfunction the efficacy of a pulse of Methylprednisolone IV for 3 days at diagnosis followed by Prednisone per os versus placebo IV followed by placebo per os in association with conventional HF therapy on the occurrence of Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF < 50% and/or Global Longitudinal Strain (GLS) < -16% between baseline (D-2) and at 6 months (M6).
Study Design
- Allocation
- Randomized
- Primary Purpose
- Corticoid Therapy in Acute Myocarditis
- Masking
- Double (Monitor, Investigator, Subject)
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age ≥ 18 years
- •Written signed informed consent
- •Affiliation to the French health care system (Sécurité Sociale) or to another social protection scheme with the exception of State Medical Aid (Aide Médicale de l’Etat AME)
- •Active myocarditis defined by (all items are required): 1- Chest pain and/or heart failure and/or syncope and/or sustained ventricular arrhythmias and/or aborted sudden death and/or cardiogenic shock and/or ECG modification (atrioventricular block or bundle branch block or sinus arrest or ST or T waves change or ventricular arrhythmia or atrial fibrillation or abnormal Q waves), 2- And troponin rise (1,5 times the normal range) and 3- And diagnosis of active myocarditis on Cardiac Magnetic Resonance (according to Lake-Louise criteria) or by histological evidence on endomyocardial biopsy (Dallas’s criteria)
- •Left-ventricular dysfunction defined as LVEF < 50% and/or GLS < -16% assessed with 2D-TTE
- •Normal coronary angiography or CT Scan (without stenosis > 50%) during the previous year
Exclusion Criteria
- •Active coronary disease
- •Other auto-immune or inflammatory disease requiring corticosteroids treatment within 6 months before enrolment
- •Pregnancy or breastfeeding
- •Woman of childbearing potential without effective method of birth control
- •Contra-indication linked to auxiliary drugs according to respective SmPC
- •Patient deprived of liberty or under Curatorship/Tutorship, safeguard of justice, according to French law
- •According to the opinion of the investigator, foreseeable inability to respect the protocol (understanding of research, ability to go to hospital, ability to take oral treatment, etc.
- •Patient not speaking or understanding French
- •Concomitant participation in another clinical trial on medical product for human use, to a clinical investigation on a medical device, to interventional study involving human participants or in the exclusion period at the end of a previous clinical trial on medical product for human use, a clinical investigation on a medical device, or study involving human participants. Participation in non-interventional research is permitted.
- •Any medical and/or cognitive condition which limits the ability of participant to participate in study
- •Contra-indication linked to steroids (Methylprednisolone and Prednisone) according to SmPC: 1- Any infectious condition excluding the specified therapeutic indications of Methylprednisolone and Prednisone, 2- Certain evolving viruses (notably hepatitis, herpes, chickenpox, shingles), 3- Psychotic states not yet controlled by treatment, 4- Recent live vaccines or live attenuated vaccines in patients receiving dosages greater than 20 mg/day of prednisone equivalent for more than two weeks and during the 3 months following the cessation of corticosteroid therapy (risk of generalized vaccine disease possibly fatal), 5- Hypersensitivity to the active substances or to any of the excipients
- •Other causes of chronic heart failure (coronary artery disease, primary valvular heart disease, congenital heart disease)
- •Other etiology of myocarditis requiring corticosteroids treatment as giant cells myocarditis, eosinophilic myocarditis and cardiac sarcoidosis or immune checkpoint inhibitor myocarditis
Outcomes
Primary Outcomes
Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF < 50% and/or Global Longitudinal Strain (GLS) < - 16% between baseline (D-2) and 6 months (M6) follow up. MACE is a combined criterion that includes all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or assistance and recurrent acute myocarditis with LV dysfunction at 6 months
Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF < 50% and/or Global Longitudinal Strain (GLS) < - 16% between baseline (D-2) and 6 months (M6) follow up. MACE is a combined criterion that includes all-cause mortality, heart failure hospitalization, sustained ventricular arrhythmia, heart transplantation or assistance and recurrent acute myocarditis with LV dysfunction at 6 months
Secondary Outcomes
- Changes in LVEF ≥ 50% at 6 months using 2D trans-thoracic echocardiography (2D-TTE) between baseline (D-2 maximum) and 6 months (M6)
- Changes in Global Longitudinal Strain (GLS) ≥ -16% at 6 months using 2D-TTE between baseline (D-2 maximum) and 6 months (M6)
- All-cause mortality
- Hospitalization for heart failure
- Sustained ventricular arrhythmia
- Heart transplantation
- Heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella device or Left Ventricular Assistance Devices (LVAD)
- Time to recurrence of acute myocarditis with LV dysfunction
- Adverse events and serious adverse events especially nosocomial infectious and duration of treatment by insulin
- Compliance to the treatment (premature ending of the treatment or proportion of non-administered doses of the treatment)
- Increased quality of life evaluated by Minnesota living with heart failure questionnaire (MLHFQ) during follow up
Investigators
Coordinating investigator
Scientific
Assistance Publique Hopitaux De Paris
Study Sites (22)
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