Corticoid Therapy in Acute Myocarditis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health

External identifiers

EU CT number

2024-510602-90-00

ClinicalTrials.gov

NCT06522100

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

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).

Secondary objectives 11

1. To compare between the two arms during the follow-up of 6 months after inclusion and randomization visit (D0) : improvement in LVEF ≥ 50% between baseline (D-2 maximum) and 6 months (M6)
2. To compare between the two arms during the follow-up of 6 months after inclusion and randomization visit (D0) : global Longitudinal Strain (GLS) ≥ -16% between baseline (D-2 maximum) and 6 months (M6)
3. All-cause mortality
4. Heart failure hospitalization
5. Sustained ventricular arrhythmia
6. Heart transplantation
7. Heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella device or Left Ventricular Assistance Devices (LVAD)
8. Recurrence of acute myocarditis with LV dysfunction
9. Safety of adverse events including nosocomial infection and the appearance of insulin-dependent diabetes
10. Adherence to the treatment regimen
11. Evaluate quality of life using Minnesota living with heart failure questionnaire (MLHFQ)

Conditions and MedDRA coding

Patients presenting with acute myocarditis proven by cardiac magnetic resonance imaging (CMRi) or by histological evidence on endomyocardial biopsy (EMB)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. Written signed informed consent
3. 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)
4. 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)
5. Left-ventricular dysfunction defined as LVEF < 50% and/or GLS < -16% assessed with 2D-TTE
6. Normal coronary angiography or CT Scan (without stenosis > 50%) during the previous year

Exclusion criteria 13

1. Active coronary disease
2. Patient deprived of liberty or under Curatorship/Tutorship, safeguard of justice, according to French law
3. 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.
4. Patient not speaking or understanding French
5. 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.
6. Any medical and/or cognitive condition which limits the ability of participant to participate in study
7. 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
8. Other causes of chronic heart failure (coronary artery disease, primary valvular heart disease, congenital heart disease)
9. Other etiology of myocarditis requiring corticosteroids treatment as giant cells myocarditis, eosinophilic myocarditis and cardiac sarcoidosis or immune checkpoint inhibitor myocarditis
10. Other auto-immune or inflammatory disease requiring corticosteroids treatment within 6 months before enrolment
11. Pregnancy or breastfeeding
12. Woman of childbearing potential without effective method of birth control
13. Contra-indication linked to auxiliary drugs according to respective SmPC

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 11

1. Changes in LVEF ≥ 50% at 6 months using 2D trans-thoracic echocardiography (2D-TTE) between baseline (D-2 maximum) and 6 months (M6)
2. Changes in Global Longitudinal Strain (GLS) ≥ -16% at 6 months using 2D-TTE between baseline (D-2 maximum) and 6 months (M6)
3. All-cause mortality
4. Hospitalization for heart failure
5. Sustained ventricular arrhythmia
6. Heart transplantation
7. Heart assistance by extracorporeal membrane oxygenation (ECMO), Intra-aortic balloon pump (IABP), Impella device or Left Ventricular Assistance Devices (LVAD)
8. Time to recurrence of acute myocarditis with LV dysfunction
9. Adverse events and serious adverse events especially nosocomial infectious and duration of treatment by insulin
10. Compliance to the treatment (premature ending of the treatment or proportion of non-administered doses of the treatment)
11. Increased quality of life evaluated by Minnesota living with heart failure questionnaire (MLHFQ) during follow up

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications