Myocarditis Therapy with Steroids in patients with a Mildly Reduced ejection fraction (MYTHS-MR)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antwerp University Hospital

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Dec 2024 → ongoing

Decision date (initial)

2024-02-06

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Italian Ministry of Health (GR-2019-12368506) · Fonds Wetenschappelijk Onderzoek (Junior Research Project by FWO Call 2021, application nr G034622N)

External identifiers

EU CT number

2022-501547-33-01

ClinicalTrials.gov

NCT05974462

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective is to demonstrate an increase in the rate of the primary composite endpoint (LVEF ≥55% or an absolute increase in LVEF≥10% on echocardiogram after 5 days from randomization) in patients treated with pulsed corticosteroid therapy vs. standard therapy.

Secondary objectives 1

1. to demonstrate superiority of treatment with corticosteroids when compared to maximal supportive therapy.

Conditions and MedDRA coding

Acute myocarditis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 18 years or older and below 70 years (18-69 years)
2. LVEF<50% and LV-EDD<56 mm (parasternal long-axis view) on echocardiogram
3. Increased troponin (3x URL) at the time of randomization
4. Clinically suspected myocarditis with onset of cardiac symptoms within 3 weeks from randomization;
5. Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven
6. Randomization within 120 hours from hospital admission
7. Endomyocardial biopsy (EMB) is not considered necessary before randomization and performing EMB is based on the decision of the local team
8. Patient has voluntarily signed and dated an informed consent form (ICF), approved by an Ethics Committee (EC) or institutional review board (IRB), after the nature of the study has been explained and the patient has had the opportunity to ask questions.

Exclusion criteria 15

1. Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is assumed useful. Patients in whom a systemic autoimmune disorder will be diagnosed during hospitalization will be included in the study if randomized, including patients with a diagnosis of cardiac sarcoidosis or GCM). Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis
2. Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis)
3. Participants involved in another clinical trial
4. Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age
5. Any other significant disease with expected life expectancy <12 months (i.e., evidence of irreversible severe brain injury) or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial
6. If LVEF<41%, an N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a B-type natriuretic peptide (BNP) concentration of 400 pg/mL or more; (if LVEF 41%-<50% any NT-proBNP or BNP concentration is allowed).
7. Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies
8. Contraindication to corticosteroids, including history of previous (steroid) psychosis, allergies to this medication and its excipients;
9. Patients with persistent peripheral eosinophilia (persistent eosinophil count >7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization
10. Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents
11. Previously known chronic cardiac disease
12. Evidence of active bacterial or fungal infectious disease (presence of fever or increased C-reactive protein are not considered exclusion criteria), or suspected bacterial/fungal infection associated with increased levels of procalcitonin (cut-off >10 ng/mL), if the laboratory exam is available in the center
13. Known chronic infective disease, such as HIV infection or tuberculosis
14. Out of hospital cardiac arrest before randomisation
15. Contraindication for CMRI

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective is to demonstrate an increase in the rate of the primary composite endpoint (LVEF >55% or increase of 10%) in patients treated with pulsed corticosteroid therapy vs. standard therapy and maximal supportive care.

Secondary endpoints 21

1. The main secondary composite endpoint is defined as the reduction in the proportion of patients with LVEF<55% AND/OR LV dilation on 6-month cardiac magnetic resonance imaging (CMRI) (CMRI clips will be centrally reviewed in a blind fashion by readers)
2. Proportion of patients with LV dilation on 6-months CMRI
3. Proportion of patients with LVEF<55% on 6-month CMRI
4. LGE burden (% of mass) on 6 month CMRI
5. Composite endpoint defined as the time from randomization to the first event ((1) all-cause death or (2) HTx or (3) long-term LVAD implantation, or (5) first rehospitalization due to HF or ventricular arrhythmias, or advanced AV block) occurring within 6 months and 2 years
6. Mortality: Time from randomization to all-cause death within 6 months and 2 years
7. Time from randomization tot hospitalization for heart failure within 6 months and 2 years
8. Composite endpoint of presence of NSVT OR burden of PVC`s>10% on 24 hour ECG ambulatory monitoring, performed at 6 months follow-up
9. Burden of PVCs (% of total heart beats) on 24 hour holtermonitoring, performed at 6 months follow-up
10. Presence of NSVT on 24 hour holtermonitoring performed at 6 months follow-up
11. Quality of life and health assessment at 2 and 6 months follow-up using the EuroQol 5-dimension, 5 level questionnaire
12. Recurrence of acute myocarditis at six months and 2 years
13. Hospitalization due to recurrence of AM, pericarditis or recurrence of chest pain or atrial fibrillation
14. In-hospital composite endpoint, defined as the proportion of patients who experience at least one of the following events during index hospitalization: 1. all-cause death, or 2. Htx, or 3. long-term LVAD implant, or 4. need for an upgrading of the t-MCS, or 5. a VT/VF treated with DC shock (excluding VT/VF in patients on t-MCS other than IABP.
15. relative reduction of troponin levels after 5 days from randomization
16. Reduction in heart rate on ECG after 3 days from randomization
17. increase in LVEF on echocardiogram after 5 days from randomization
18. Number of days in the hospital
19. number of days on the ICU
20. Need for inotropes
21. number of days on t-MCS

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antwerp University Hospital

Sponsor organisation

Antwerp University Hospital

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Antwerp University Hospital

Contact name

Studiesecretariaat cardiologie

Public contact point

Organisation

Antwerp University Hospital

Contact name

Studiesecretariaat cardiologie

Sponsor responsibilities

Article 77 compliance

Antwerp University Hospital

Contact point sponsor

Antwerp University Hospital

Article 77 implementation

Antwerp University Hospital

Locations

4 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 25 files

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

Application history

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