Randomised placebo controlled clinical trial of efficacy of MYOcardial protection in postacute inFLAMmatory cardiac involvEment due to COVID-19 (MYOFLAME-19)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Goethe University Frankfurt

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

13 Dec 2022 → 24 Apr 2026

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516463-84-00

EudraCT number

2022-001682-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective is to determine the efficacy of a combined immunosuppressive and antiremodelling therapy in COVID-19 related inflammatory cardiovascular involvement by CMR to reduce inflammatory myocardial injury compared to placebo.
The primary safety objective is to demonstrate that a combined immunosuppressive and antiremodelling therapy in proposed doses in this patient population is safe.

Secondary objectives 1

1. The secondary objectives are to determine the efficacy of a combined immunosuppressive and antiremodelling therapy in COVID-19 related inflammatory cardiovascular involvement by CMR to reduce inflammatory myocardial injury compared to placebo by improvement in other clinical parameters.

Conditions and MedDRA coding

Inflammatory cardiovascular involvement due to COVID-19, defined by Cardiovascular magnetic resonance imaging

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participants ≥ 18 years
2. Participants with documented recent COVID19 infection (> 4 weeks)
3. Post-acute sequelae of SARS-CoV-2 infection (PASC) Syndrome, defined by persistence or new symptoms, not present prior to the infection.
4. Cardiovascular magnetic resonance imaging (CMR) evidence of inflammatory cardiac involvement at baseline (BL) by any of the following criteria: o Increased native T1≥ 1130 ms at 3.0 Tesla (or 1030 ms at 1.5 Tesla) and/or; o Increased native T2 ≥39.5 ms at 3.0 Tesla (or 49.5 at 1.5 Tesla)and/or o present non-ischaemic myopericardial Late gadolinium enhancement (LGE) and/or; o Left ventricular ejection fraction (LVEF) ≥45 - ≤50%.
5. Willingness to comply with the study procedures and study protocol.

Exclusion criteria 16

1. Severe course of acute COVID illness requiring hospitalisation
2. Participants currently participating in an investigational study or for whom participation is planned.
3. Unable to provide written informed consent
4. Known allergy to or intolerance of the study medications
5. Symptomatic hypotension (systolic blood pressure less than 90 mm Hg), not reversible with oral hydration
6. Any previous or current use of ACE inhibitors, AR Blockers
7. Any previous oral prednisolone, or any other immunosuppressive or biological treatment (within prior 10 weeks)
8. History or CMR evidence of preexisting heart disease, including: a. Known cardiac impairment with LVEF ≤44% b. Congestive heart failure (NYHA III-IV) c. Active heart failure treatment d. Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease e. Persistent or permanent atrial fibrillation or significant heart rhythm abnormalities. f. Congenital or clinically relevant valvular heart disease (moderate or severe) g. Specific cardiomyopathy (hypertrophic, hypertensive heart disease, amyloidosis, previous myocarditis, non-ischaemic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, noncompaction cardiomyopathy, etc).
9. Known significant concomitant diseases that are likely to interfere with the evaluation of the participant’s safety and of the study outcome (e.g. diabetes, lung or hepatic disease, epilepsy, psychiatric disorders, renal disease with a current estimated GFR <30 mL/min/1.73 m² using MDRD formula, chronic systemic infection or immunocompromise)
10. Exceeding scanner bore and table-holding capacity: Weight >125 kg, BMI > 35 kg/m2
11. Contraindications to contrast-enhanced CMR imaging, e.g. a. MR-unsafe implantable device b. known allergy to gadolinium-based contrast agent (CBGA)
12. For female participants: a. Pregnant or breastfeeding women b. Women of childbearing potential not willing to use highly effective contraception (as defined in 18.2.13)
13. Known alcohol, drug or chemical abuse
14. Participants currently participating in an investigational study or for whom participation is planned.
15. Unable to provide written informed consent.
16. Participants with CMR evidence of structural heart disease or incidental heart rhythm abnormalities will be advised to see their own doctor for further investigation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is absolute LVEF change to baseline at W16, measured by CMR, compared between the verum and placebo group by absolute treatment difference

Secondary endpoints 14

1. The secondary endpoints include the following continuous endpoints, where "changes" refer to the difference between baseline and W16 (BL, absolute and in %):
2. Mean Late gadolinium enhancement (LGE) extent (%) and change thereof compared to BL
3. CPET (achieved Work Rate, VO2max, VCO2 max, RER, AT, slope) and change thereof compared to BL
4. Mean T1 and T2 values (ms) and change thereof compared to BL
5. Mean LV and RV volumes (ml/m2) and LV mass (g/m2) as well as derived parameters and change thereof compared to BL
6. Mean Myocardial strain (%) and change thereof compared to BL
7. Mean Pulse wave velocity (m/s) and change thereof compared to BL
8. Aortic wall thickness (LGE, mm); and change thereof compared to BL
9. Average Symptom Score and change thereof compared to BL
10. Compliance: Frequency of prescribed medication consumed, participants diary and drug adherence, total cumulative steroid dose;
11. Tolerance: number of participants who required dose reduction or treatment cessation due to side effects, especially due to o Hypotension o Unblinding due to emergency safety issues
12. Number of Responders by achieving: o partial response: a normal CMR result is defined as normal T1 and T2, normal gender-age predicted LVEF, non-dilated LV o total response: in addition to the above absence of LGE
13. Proportion of participants with HF or MACE after 1 year
14. 1 year Event-free survival

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Goethe University Frankfurt

Sponsor organisation

Goethe University Frankfurt

Address

Theodor-Stern-Kai 7

City

Frankfurt Am Main

Postcode

60590

Country

Germany

Scientific contact point

Organisation

Goethe University Frankfurt

Contact name

Dr. Valentina Puntmann

Public contact point

Organisation

Goethe University Frankfurt

Contact name

Dr. Valentina Puntmann

Third parties 2

Locations

2 EU/EEA countries · 3 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 11 files

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

Application history

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