NCT05619653: MYOFLAME-19

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

Active, enrolled Phase 3 Last updated 9 December 2025

What this trial tests

Phase 3 trial testing Prednisolone in COVID-19 Associated Cardiac Involvement in 279 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

12 December 2022

Primary endpoint
8 August 2025

31 March 2026

Quick facts

Lead sponsor	Valentina Puentmann
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	279
Start date	12 December 2022
Primary completion	8 August 2025
Estimated completion	31 March 2026
Sites	5 locations across Austria, Germany

Drugs / interventions tested

• Prednisolone — full drug profile →
• Losartan (losartan) — full drug profile →

Conditions studied

• COVID-19 Associated Cardiac Involvement — all drugs for COVID-19 Associated Cardiac Involvement →
• Remodeling, Left Ventricle — all drugs for Remodeling, Left Ventricle →
• Remodeling, Vascular — all drugs for Remodeling, Vascular →
• Left Ventricular Dysfunction — all drugs for Left Ventricular Dysfunction →

Sponsor

Valentina Puentmann

Who can join

Adults 18 to 65, any sex, with COVID-19 Associated Cardiac Involvement or Remodeling, Left Ventricle. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Long COVID or Postacute sequelae of COVID-19 infection (PASC) are increasingly recognised complications, 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 (POTS, exertional tachycardia).

Pathophysiologically, Long COVID relates to small vessel disease (endothelial dysfunction) vascular dysfunction and consequent tissue organ hypoperfusion due to ongoing immune dysregulation. Active organs with high oxygen dependency are most affected (heart, brain, kidneys, muscles, etc.). Thus, cardiac symptoms are often accompanied by manifestations of other organ systems, including fatigue, brain fog, kidney problems, myalgias, skin and joint manifestations, etc, now commonly referred to as the Long COVID or PASC syndrome.

Phenotypically, PostCOVID Heart involvement is characterised by chronic perivascular and myopericardial inflammation. We and others have shown changes using sensitive cardiac MRI imaging that relate to cardiac symptoms (Puntmann et al, Nature Medicine 2022; Puntmann et al, JAMA Cardiol 2020; Summary of studies included in 2022 ACC PostCOVID Expert Consensus Taskforce Development Statement, JACC 2022, references below).

Early intervention with immunosuppression and antiremodelling therapy may reduce symptoms and development of 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. The benefits of early initiations of antiremodelling therapy to reduce symptoms of exercise intolerance are well recognised, but not commonly employed outside the classical cardiology contexts, such as heart failure or hypertension. As most patients with inflammatory heart disease only have mild 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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.
   Shumliakivska M, Luxán G, Hemmerling I, Scheller M, et al · · 2024 · cited 56× · PMID 38242884 · DOI 10.1038/s41467-023-43003-w
2. Cardiac Involvement Due to COVID-19: Insights from Imaging and Histopathology.
   Puntmann VO, Shchendrygina A, Bolanos CR, Madjiguène Ka M, et al · · 2023 · cited 13× · PMID 37942208 · DOI 10.15420/ecr.2023.02
3. Improvement of Symptoms and Cardiac Magnetic Resonance Abnormalities in Patients with Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome (PASC-CVS) after Guideline-Oriented Therapy.
   Gyöngyösi M, Hasimbegovic E, Han E, Zlabinger K, et al · · 2023 · cited 3× · PMID 38137533 · DOI 10.3390/biomedicines11123312
4. Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints.
   Puntmann VO, Beitzke D, Kammerlander A, Voges I, et al · · 2025 · cited 2× · PMID 39481808 · DOI 10.1016/j.jocmr.2024.101121
5. Trajectories of functional and structural myocardial parameters in post-COVID-19 syndrome-insights from mid-term follow-up by cardiovascular magnetic resonance.
   Gröschel J, Grassow L, van Dijck P, Bhoyroo Y, et al · · 2024 · cited 2× · PMID 38628318 · DOI 10.3389/fcvm.2024.1357349