MYOFLAME-19: Myocardial Protection in Patients With Post-acute Inflammatory Cardiac Involvement Due to COVID-19

Sponsor

Valentina Puentmann (Other)

Overall Status

Recruiting

CT.gov ID

NCT05619653

Collaborator

Bayer (Industry), Alcedis GmbH (Industry)

280

Enrollment

Location

Arms

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Postacute sequelae of COVID-19 infection (PASC) are increasingly recognised complications and are defined by lingering symptoms, not present prior to the infection, typically persisting for more than 4 weeks. Cardiac symptoms due to post-acute inflammatory cardiac involvement affect a broad segment of people, who were previously well and may have had only mild acute illness (PASC-cardiovascular syndrome, PASC-CVS). Symptoms may be contiguous with the acute illness, however, more commonly they occur after a delay. Symptoms related to the cardiovascular system include exertional dyspnoea, exercise intolerance chest tightness, pulling or burning chest pain, and palpitations. Phenotypically, it is characterised by chronic perivascular and myopericardial inflammation. Cardiac symptoms may be accompanied by manifestations of other organ systems, including fatigue, brain fog, myalgias, skin and joint manifestations, etc, now commonly referred to as the Long COVID or PASC syndrome.

Early intervention with immunosuppression and antiremodelling therapy may reduce symptoms and myocardial impairment, by minimising the disease activity and inducing disease remission. Low dose maintenance therapy may help to maintain the disease activity at the lowest possible level. Clinical trials of immunosuppression in patients with viral myocarditis in advanced stages of heart failure have not shown an improved outcome, however there was an improvement of LVEF with antiremodelling therapy in patients with reduced function. The benefits of early initiations of antiremodelling therapy to reduce symptoms of exercise intolerance are well recognised, but not commonly employed outside the contexts of heart failure or hypertension. As most patients with inflammatory heart disease only have mild and nonspecific symptoms and few or no structural abnormalities, they are left untreated (standard of care). The aim of this study is to examine the efficacy of a combined immunosuppressive/antiremodelling therapy in patients with PASC symptoms and inflammatory cardiac involvement determined by CMR, to reduce the symptoms and inflammatory myocardial injury and thereby stop the progression to reduced LVEF, HF and death.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Inflammation Remodeling, Left Ventricle Remodeling, Vascular Left Ventricular Dysfunction Exercise Intolerance	Drug: Prednisolone Drug: Losartan	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

multicentre randomised double-blind, placebo-controlled clinical trial 1:1 randomisationmulticentre randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Placebo

Primary Purpose:

Treatment

Official Title:

Randomised Placebo Controlled Clinical Trial of Efficacy of MYOcardial Protection in Patients With Postacute inFLAMmatory Cardiac involvEment Due to COVID-19

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Verum Prednisolone and Losartan	Drug: Prednisolone randomised double-blind, placebo-controlled clinical trial 1:1 randomisation Drug: Losartan randomised double-blind, placebo-controlled clinical trial 1:1 randomisation
Placebo Comparator: Placebo Placebo 1 and Placebo 2	Drug: Prednisolone randomised double-blind, placebo-controlled clinical trial 1:1 randomisation Drug: Losartan randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Arm

Intervention/Treatment

Active Comparator: Verum

Prednisolone and Losartan

Drug: Prednisolone

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Drug: Losartan

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Placebo Comparator: Placebo

Placebo 1 and Placebo 2

Drug: Prednisolone

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Drug: Losartan

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Outcome Measures

Primary Outcome Measures

Left ventricular ejection fraction [16 weeks]
absolute change of LVEF from baseline

Secondary Outcome Measures

Scar burden by late gadolinium enhancement (LGE) [16 weeks]
absolute change of LGE from baseline
Cardiopulmonary exercise testing (CPET) [16 weeks]
absolute change of achieved VO2max from baseline
Mean T1 and T2 mapping [16 Weeks]
absolute change in T1 and T2 mapping values (ms) from baseline
LV mass (g/m2) [16 Weeks]
absolute change of measures from baseline
LV strain % [16 Weeks]
absolute change of measures from baseline
Aortic stiffness (PWV) [16 Weeks]
absolute change of measures from baseline
Aortic wall imaging (LGE) [16 Weeks]
absolute change of measures from baseline
Average Symptom Score (RAND 36) [16 Weeks]
change thereof compared to baseline
HF and MACE Endpoints [1 and 5 years]
proportion of patients with endpoints

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients ≥ 18 years
Patients with documented recent COVID19 infection (>4 weeks and <6 months)
PASC Syndrome, defined by persistence or new symptoms, not present prior to the infection.
CMR evidence of inflammatory cardiac involvement at BL by any of the following criteria:
Increased native T1≥ 1130 ms at 3.0 Tesla (or 1030 ms at 1.5 Tesla) and/or;
Increased native T2 ≥39.5 ms at 3.0 Tesla (or 49.5 at 1.5 Tesla) and/or
present non-ischaemic myopericardial LGE and/or;
LVEF ≥45 - ≤50%.
Willingness to comply with the study procedures and study protocol

Exclusion Criteria:

Severe acute COVID illness requiring hospitalisation
Known allergy to or intolerance of the study medications
Symptomatic hypotension (systolic blood pressure less than 90 mm Hg), not reversible with oral hydration
Any previous or current use of ACE inhibitors, AR Blockers
Any previous oral prednisolone, or any other immunosuppressive or biological treatment (within 6 months)
History or CMR evidence of pre-existing significant heart disease, including:

Known cardiac impairment with LVEF ≤44%
Congestive heart failure (NYHA III-IV)
Active heart failure treatment
Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
Persistent or permanent atrial fibrillation or significant heart rhythm abnormalities
Congenital or clinically relevant valvular heart disease (moderate or severe)
Specific cardiomyopathy (hypertrophic, hypertensive heart disease, amyloidosis, previous myocarditis, non-ischaemic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, non-compaction cardiomyopathy, etc).

Known significant concomitant diseases that are likely to interfere with the evaluation of the patient'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)
Exceeding scanner bore and table-holding capacity: Weight >125 kg, BMI > 35 kg/m2
Contraindications to contrast-enhanced CMR imaging, e.g.

MR-unsafe implantable device
known allergy to gadolinium-based contrast agent (CBGA)

For female participants:

Pregnant or breastfeeding women
Persons of childbearing potential not willing to use effective contraception (defined as PEARL index <1 - e.g. contraceptive pill, IUD)

Known alcohol, drug or chemical abuse
Patients currently participating in an investigational study or for whom participation is planned.
Unable to provide written informed consent

Patients with CMR evidence of structural heart disease or incidental heart rhythm abnormalities will be advised to see their own doctor for further investigation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for experimental and translational cardiovascular imaging	Frankfurt Am Main	Hessen	Germany	60596

Sponsors and Collaborators

Valentina Puentmann
Bayer
Alcedis GmbH

Investigators

Principal Investigator: Valentina Puntmann, MD, PhD, University Hospital Frankfurt
Principal Investigator: Eike Nagel, MD, PhD, University Hospital Frankfurt