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

NCT05619653 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: MYOFLAME-192022-001682-12
• Study Type: interventional
• Target: 279
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Exercise Intolerance; Vascular Inflammation; Microvascular Angina; Long COVID; Myocarditis, Pericarditis; COVID-19 Associated Cardiac Involvement; Remodeling, Left Ventricle; Remodeling, Vascular; Left Ventricular Dysfunction

Keywords

long COVID; postCOVID; endothelial dysfunction; myocarditis

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction

  absolute change of LVEF from baseline

  16 weeks

Secondary Outcomes (12)

• Scar burden by late gadolinium enhancement (LGE)

  16 weeks

• Cardiopulmonary exercise testing (CPET)

  16 weeks

• Mean T1 and T2 mapping

  16 Weeks

• LV Volume (ml/m2) and LV mass (g/m2)

  16 Weeks

• LV strain %

  16 Weeks

Study Arms (2)

Verum

ACTIVE COMPARATOR

Prednisolone and Losartan

Drug: Prednisolone; Drug: Losartan

Placebo

PLACEBO COMPARATOR

Placebo 1 and Placebo 2

Drug: Prednisolone; Drug: Losartan

Interventions

Prednisolone DRUG

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

Placebo; Verum

Losartan DRUG

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

Placebo; Verum

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years
• Patients with documented recent COVID19 infection (\>4 weeks)
• 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

You may not qualify if:

• 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 prior 10 weeks)
• 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

Sponsors & Collaborators

• Valentina Puentmann: lead
• Bayer: collaborator
• Alcedis GmbH: collaborator

Study Sites (5)

University Medical Centre Vienna

Vienna, 1090, Austria

Location

Institute for experimental and translational cardiovascular imaging

Frankfurt am Main, Hesse, 60596, Germany

Location

University Hospital Greifswald

Greifswald, 17475, Germany

Location

University Hospital Schleswig-Holstein, Campus KIEL

Kiel, 24105, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

Related Publications (4)

• Puntmann VO, Martin S, Shchendrygina A, Hoffmann J, Ka MM, Giokoglu E, Vanchin B, Holm N, Karyou A, Laux GS, Arendt C, De Leuw P, Zacharowski K, Khodamoradi Y, Vehreschild MJGT, Rohde G, Zeiher AM, Vogl TJ, Schwenke C, Nagel E. Long-term cardiac pathology in individuals with mild initial COVID-19 illness. Nat Med. 2022 Oct;28(10):2117-2123. doi: 10.1038/s41591-022-02000-0. Epub 2022 Sep 5.

  PMID: 36064600 BACKGROUND

• Writing Committee; Gluckman TJ, Bhave NM, Allen LA, Chung EH, Spatz ES, Ammirati E, Baggish AL, Bozkurt B, Cornwell WK 3rd, Harmon KG, Kim JH, Lala A, Levine BD, Martinez MW, Onuma O, Phelan D, Puntmann VO, Rajpal S, Taub PR, Verma AK. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 May 3;79(17):1717-1756. doi: 10.1016/j.jacc.2022.02.003. Epub 2022 Mar 16. No abstract available.

  PMID: 35307156 BACKGROUND

• Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, Shchendrygina A, Escher F, Vasa-Nicotera M, Zeiher AM, Vehreschild M, Nagel E. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Nov 1;5(11):1265-1273. doi: 10.1001/jamacardio.2020.3557.

  PMID: 32730619 BACKGROUND

• Puntmann VO, Beitzke D, Kammerlander A, Voges I, Gabbert DD, Doerr M, Chamling B, Bozkurt B, Kaski JC, Spatz E, Herrmann E, Rohde G, DeLeuw P, Taylor L, Windemuth-Kieselbach C, Harz C, Santiuste M, Schoeckel L, Hirayama J, Taylor PC, Berry C, Nagel E. Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints. J Cardiovasc Magn Reson. 2025 Summer;27(1):101121. doi: 10.1016/j.jocmr.2024.101121. Epub 2024 Oct 29.

  PMID: 39481808 BACKGROUND

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Ventricular Remodeling; Vascular Remodeling; Ventricular Dysfunction, Left; Microvascular Angina; Post-Acute COVID-19 Syndrome; Myocarditis; Pericarditis

Interventions

Prednisolone; Losartan

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Angina Pectoris; Myocardial Ischemia; Vascular Diseases; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Cardiomyopathies

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Valentina Puntmann, MD, PhD

  Goethe University Frankfurt

  PRINCIPAL INVESTIGATOR

• Eike Nagel, MD, PhD

  Goethe University Frankfurt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

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

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: November 17, 2022
• Study Start: December 12, 2022
• Primary Completion: August 8, 2025
• Study Completion: March 31, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (4)