Pulse corticosteroids or/and Immunoglobulins to treat fulminant Myocarditis: a double-blind randomized controlled adaptive trial (The CORIUM study)

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)

2025-01-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC-N 2021/French Ministry of Health

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess at day 28 the efficacy of pulse bolus corticosteroids or pulse bolus corticosteroids and IVIG vs double placebo on a composite hierarchical outcome of mortality or heart transplantation/ long-term ventricular assist device (VAD)/persisting t-MCS and the number of days alive between randomization and day 28 without t-MCS and inotropes.

Secondary objectives 3

1. 1) Assess the efficacy of pulse bolus corticosteroids and IVIG on: - Mortality - Duration of t-MCS and inotropes support - Cardiac fufnction - Ventricular arrhythmia - Atrioventricular block - Hemodynamic and organs dysfunction - Duration of ICU stay and hospitalization
2. 2) Assess the safety of pulse bolus corticosteroids and IVIG in FM
3. 3) Assess the homogeneity of pulse bolus corticosteroids and IVIG on mortality in predefined subgroups (patients on t-MCS, COVID-19 related multisystem inflammatory syndrome)

Conditions and MedDRA coding

Fulminant myocarditis

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

See L1_SIS and ICF -Patient-utilisation-données_2023-506599-28-00

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Fulminant myocarditis defined by • the acute illness (<1 month from symptom onset), • hemodynamic compromise due to cardiogenic shock or electrical storm, • elevated plasma cardiac troponin > twice normal value • need for hemodynamic support (inotropes or temporary mechanical circulatory support) for less than 72 hours in the absence of an ischemic cause or other pre-existing cardiomyopathies Noticeably, a coronary angiogram should be performed in patients ≥40 years of age when myocarditis has not been proven histologically. Besides, an endomyocardial biopsy will not be mandatory to fulfill the definition of fulminant myocarditis.
2. 2. Signed informed consent from the patient, a close relative or surrogate or a family member or a legal representative for minor patient. • Adult : According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patientis unable to give his/her consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow. • Minor : According to the specifications of emergency inclusion, randomization could be performed when legal representative are absent. Legal representative consent will be asked as soon as possible after randomization
3. 3. Social security registration (AME excluded)

Exclusion criteria 13

1. 1. Age <15
2. 2. Pregnancy or breastfeeding or baby delivery <6 months
3. 3. Initiation of inotropes or temporary mechanical circulatory support >72 hours
4. 4. Resuscitation >20 minutes (cumulative low-flow time > 20 minutes )
5. 5. Pre-existing ischemic or dilated cardiomyopathy
6. 6. Known systemic autoimmune disorder or other conditions requiring immunosuppression
7. 7. Patients with peripheral eosinophilia (≥1000 G/L)
8. 8. Myocarditis associated with anti-cancer immune checkpoint inhibitor agents
9. 9. Active severe bacterial or fungal infectious disease
10. 10. Patient moribund on the day of randomization, SAPS II >90
11. 11. Contraindication or allergies to corticosteroids or immunoglobulins or any components of the formulations or their excipients
12. 12. Patients already on corticosteroids or receiving IVIG
13. 13. Participation in another interventional study or being in the exclusion period at the end of a previous study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - A hierarchical composite outcome assessed at day 28 of mortality or heart transplantation/VAD/persisting t-MCS and the number of days alive without t-MCS and inotropes within the 28 days following randomization

Secondary endpoints 11

1. Mortality at day 28/60/90
2. - VAD or/and heart transplant at day 28/60/90
3. - Number of t-MCS-free days at day 28
4. - Number of inotropes-free days at day 28
5. - Time to improvement in left ventricular function assessed by echocardiography at D3/D7/D14/D28 following randomization
6. - Time to normalize troponin and N-terminal pro–B-type natriuretic peptide within 14 days after randomization
7. - Incidence of drugs side effects (nosocomial infections, significant gastrointestinal bleeding, renal insufficiency, acute delirium leading to the use of neuroleptic agents)
8. - Proportion of patients with left ventricular ejection fraction (LVEF) < 55% and/or left ventricular dilatation at 28-day
9. - Proportion of patients with at least one episode of ventricular arrhythmia at day-28
10. - Proportion of patients with at least one episode of atrioventricular block (degree II and III) or sinoatrial, atrioventricular or intraventricular block
11. - The proportion of patients with LVEF<55%, left ventricular dilatation, and late gadolinium enhancement at 6 months evaluated by cardiac magnetic resonance imaging

Investigational products

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

Test 3

Placebo 1

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 · 8 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 20 files

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

Application history

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