Corticoid Therapy in Acute Myocarditis

NCT06522100 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: APHP230855
• Study Type: interventional
• Target: 420
• Locations: 0 countries
• Sites: N/A

Brief Summary

Refer to the "Detailed Description" section.

Conditions

Acute Myocarditis

Keywords

Acute myocarditis; Corticoids; Left ventricular dysfunction

Outcome Measures

Primary Outcomes (1)

• Efficacy of treatments

  Major Cardiovascular Events (MACE) and/or persistence of left ventricular dysfunction defined as LVEF \< 50% and/or Global Longitudinal Strain (GLS) \< - 16%. 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.

  6 months

Secondary Outcomes (11)

• Changes in LVEF ≥ 50%

  6 months

• Global Longitudinal Strain (GLS) ≥ -16%

  6 months

• All-cause mortality

  6 months

• Heart failure hospitalization

  6 months

• Sustained ventricular arrhythmia

  6 months

Study Arms (2)

Experimental group

EXPERIMENTAL

Randomization in experimental group in addition to conventional HF therapy for 6 months.

Drug: Intravenous administration of Methylprednisolone; Drug: Oral Prednisone

Control group

PLACEBO COMPARATOR

Randomization in control group in addition to conventional HF therapy for 6 months.

Drug: Perfusion of placebo; Drug: Oral Prednisone placebo

Interventions

Intravenous administration of Methylprednisolone DRUG

Patients will take intravenous administration of Methylprednisolone (500mg/100ml by IV over 30 minutes per day) for 3 days.

Experimental group

Oral Prednisone DRUG

After intravenous administration of Methylprednisolone patients will take by oral Prednisone 1mg/kg per day once a day (with a maximum dose of 90 mg per day for patients weighing \> 90kg) for 1 month, followed with a progressive decrease of 10 mg Prednisone every 15 days until a dose of 10mg per day during 15 days (= stop).

Experimental group

Perfusion of placebo DRUG

Patients will take perfusion of placebo (G5%: 100ml over 30 minutes per day) for 3 days.

Control group

Oral Prednisone placebo DRUG

After the perfusion of placebo, patients will take by oral Prednisone placebo once a day for the same duration as that required if the patient was in the investigational medicinal products group (1 month + progressive decrease).

Control group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Written signed informed consent
• Affiliation to the French health care system or to another social protection scheme with the exception of State Medical Aid
• Active myocarditis defined by (all items are required):
• Acute chest pain and/or unexplained 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)
• And troponin rise (1,5 times the normal range)
• 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

You may not qualify if:

• Active coronary disease
• 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
• 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 (included contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices)
• Patient deprived of liberty or under Curatorship/Tutorship, safeguard of justice, according to French law
• Foreseeable inability, according to the investigator, to participate in all the visits, treatments and measures provided for in the protocol
• Patient not speaking or understanding French
• 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 summary of product characteristics:
• Any infectious condition excluding the specified therapeutic indications of Methylprednisolone and Prednisone
• Certain evolving viruses (notably hepatitis, herpes, chickenpox, shingles)
• Psychotic states not yet controlled by treatment
• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

David AOUATE, Dr

CONTACT

+33 1 49 81 45 84; davidrobin.aouate@aphp.fr

Raphäelle HUGUET, Dr

CONTACT

+33 1 45 17 82 77; raphaelle.huguet@aphp.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: Phase III, prospective, randomized, placebo controlled, superiority, double blinded trial with 2 parallel groups randomized in a 1:1 ratio. Patients will be hospitalized in Cardiology or Intensive Care Unit for a suspicion of an acute myocarditis. They will have an 2D-TTE to confirm a left ventricular dysfunction (LVEF \< 50% and/or Global longitudinal strain \[GLS\] \< -16%) and a cardiac magnetic resonance imaging or an endomyocardial biopsy will be performed to prove acute myocarditis. Coronary artery disease will be excluded by coronary angiography or Cardiac CT Scan. Once diagnosis of complicated AM with left ventricular dysfunction done, investigators will have 48 hours to include the patients and randomize them. They will benefit of placebo or experimental treatment in addition of conventional treatment for 6 months. At M6, end of participation for each patients, they will benefit of cardiologist consultation with TTE and cardiac magnetic resonance imaging.

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 26, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): August 16, 2028
• Study Completion (Estimated): August 16, 2028
• Last Updated: July 29, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share