Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints
ABSTRACT: Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can...
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2025-01-01
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| Series: | Journal of Cardiovascular Magnetic Resonance |
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| author | Valentina O. Puntmann Dietrich Beitzke Andreas Kammerlander Inga Voges Dominik D. Gabbert Marcus Doerr Bishwas Chamling Biykem Bozkurt Juan Carlos Kaski Erica Spatz Eva Herrmann Gernot Rohde Philipp DeLeuw Lenka Taylor Christine Windemuth-Kieselbach Cornelia Harz Marta Santiuste Laura Schoeckel Juliana Hirayama Peter C. Taylor Colin Berry Eike Nagel |
| author_facet | Valentina O. Puntmann Dietrich Beitzke Andreas Kammerlander Inga Voges Dominik D. Gabbert Marcus Doerr Bishwas Chamling Biykem Bozkurt Juan Carlos Kaski Erica Spatz Eva Herrmann Gernot Rohde Philipp DeLeuw Lenka Taylor Christine Windemuth-Kieselbach Cornelia Harz Marta Santiuste Laura Schoeckel Juliana Hirayama Peter C. Taylor Colin Berry Eike Nagel |
| author_sort | Valentina O. Puntmann |
| collection | DOAJ |
| description | ABSTRACT: Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing. Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural heart disease, undergo standardized assessments with questionnaires, CMR imaging, and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical post-COVID inflammatory heart involvement on baseline CMR examination are randomized to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at a significance level of 0.05 significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analyzed for frequency, severity, and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analyzed. A calculated sample size is a total of 280 participants (accounting for 22 subjects (8%) drop out), randomized in 1:1 fashion to 140 in the verum and 140 placebo groups. Conclusion: Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, improve exercise tolerance, and preclude the development of cardiac impairment. |
| format | Article |
| id | doaj-art-ec5b7ea1c5c247b684dbedea24590f1c |
| institution | Kabale University |
| issn | 1097-6647 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Journal of Cardiovascular Magnetic Resonance |
| spelling | doaj-art-ec5b7ea1c5c247b684dbedea24590f1c2025-08-20T03:45:59ZengElsevierJournal of Cardiovascular Magnetic Resonance1097-66472025-01-0127110112110.1016/j.jocmr.2024.101121Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance EndpointsValentina O. Puntmann0Dietrich Beitzke1Andreas Kammerlander2Inga Voges3Dominik D. Gabbert4Marcus Doerr5Bishwas Chamling6Biykem Bozkurt7Juan Carlos Kaski8Erica Spatz9Eva Herrmann10Gernot Rohde11Philipp DeLeuw12Lenka Taylor13Christine Windemuth-Kieselbach14Cornelia Harz15Marta Santiuste16Laura Schoeckel17Juliana Hirayama18Peter C. Taylor19Colin Berry20Eike Nagel21Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, Goethe University Frankfurt, Frankfurt am Main, Germany; German Centre for Cardiovascular Research - Partner Site Rhein-Main, Rhein-Main, Germany; Corresponding author. Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, Goethe University Frankfurt, Frankfurt am Main, Germany.Department of Biomedical Imaging and Image-Guided Therapy, Division of Radiology and Nuclear Medicine, University Hospital Vienna, Vienna, AustriaDepartment of Cardiology, University Hospital Vienna, Vienna, AustriaDepartment of Cardiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; German Centre for Cardiovascular Research - Partner Site Hamburg/Kiel/Lübeck, Kiel, GermanyDepartment of Cardiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Cardiology, Angiology, and Pulmonology, Internal Intensive Care Unit, University Hospital Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research - Partner Site Greifswald, Greifswald, GermanyDepartment of Cardiology, Angiology, and Pulmonology, Internal Intensive Care Unit, University Hospital Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research - Partner Site Greifswald, Greifswald, GermanyWinters Center for Heart Failure Research, Houston, Texas, USA; Cardiovascular Research Institute, Baylor College of Medicine, DeBakey VA Medical Center, Houston, Texas, USACardiovascular Sciences, Molecular and Clinical Sciences, St George's, University of London, London, UKCardiovascular Medicine, Yale Center for Outcomes Research and Evaluation, Yale School of Medicine, 800 Howard Avenue, New Haven, Connecticut 06519, USAInstitute of Biostatistics and Mathematical Modeling, Center for Health Sciences, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Respiratory Medicine, Goethe University Frankfurt, Medical Clinic I, University Hospital, Frankfurt am Main, GermanyInfektologikum Frankfurt, Frankfurt am Main, GermanyPharmacy of the Clinical Trial Unit, Medical School, University Hospital Heidelberg, Heidelberg, GermanyAlcedis GmbH (CRO), Gießen, GermanyBayer AG, Leverkusen, GermanyBayer Pharmaceuticals LLC, Whippany, New Jersey, USABayer AG, Leverkusen, GermanyBayer Pharmaceuticals LLC, Whippany, New Jersey, USANuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, Oxford OX3 7LD, UKUniversity of Glasgow, School of Cardiovascular & Metabolic Health, BHF Glasgow Cardiovascular Research Centre (GCRC), Glasgow, UKInstitute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, Goethe University Frankfurt, Frankfurt am Main, Germany; German Centre for Cardiovascular Research - Partner Site Rhein-Main, Rhein-Main, GermanyABSTRACT: Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing. Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural heart disease, undergo standardized assessments with questionnaires, CMR imaging, and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical post-COVID inflammatory heart involvement on baseline CMR examination are randomized to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at a significance level of 0.05 significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analyzed for frequency, severity, and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analyzed. A calculated sample size is a total of 280 participants (accounting for 22 subjects (8%) drop out), randomized in 1:1 fashion to 140 in the verum and 140 placebo groups. Conclusion: Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, improve exercise tolerance, and preclude the development of cardiac impairment.http://www.sciencedirect.com/science/article/pii/S1097664724011487COVID-19Myocardial inflammationMicrovascularCardiac magnetic resonanceClinical trialImaging endpoint |
| spellingShingle | Valentina O. Puntmann Dietrich Beitzke Andreas Kammerlander Inga Voges Dominik D. Gabbert Marcus Doerr Bishwas Chamling Biykem Bozkurt Juan Carlos Kaski Erica Spatz Eva Herrmann Gernot Rohde Philipp DeLeuw Lenka Taylor Christine Windemuth-Kieselbach Cornelia Harz Marta Santiuste Laura Schoeckel Juliana Hirayama Peter C. Taylor Colin Berry Eike Nagel Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints Journal of Cardiovascular Magnetic Resonance COVID-19 Myocardial inflammation Microvascular Cardiac magnetic resonance Clinical trial Imaging endpoint |
| title | Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints |
| title_full | Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints |
| title_fullStr | Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints |
| title_full_unstemmed | Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints |
| title_short | Design and rationale of MYOFLAME-19 randomised controlled trial: MYOcardial protection to reduce post-COVID inFLAMmatory heart disease using cardiovascular magnetic resonance Endpoints |
| title_sort | design and rationale of myoflame 19 randomised controlled trial myocardial protection to reduce post covid inflammatory heart disease using cardiovascular magnetic resonance endpoints |
| topic | COVID-19 Myocardial inflammation Microvascular Cardiac magnetic resonance Clinical trial Imaging endpoint |
| url | http://www.sciencedirect.com/science/article/pii/S1097664724011487 |
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