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
{"title":"MYOFLAME-19 RCT 的设计和原理:使用 CMR终点对心肌进行保护,以减少 COVID-19 感染引起的心肌炎性心脏病。","authors":"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","doi":"10.1016/j.jocmr.2024.101121","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute COVID-19 illness and without overt structural heart disease. Cardiac 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 prior to development of myocardial injury and impairment is missing.</p><p><strong>Trial design: </strong>Prospective multicentre randomised placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodelling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no preexisting significant comorbidities or structural heart disease, undergo standardised assessments with questionnaires, CMR imaging and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical Post-COVID inflammatory involvement on baseline CMR examination are randomised 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 (LVEF) to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at the 5% 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 analysed 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 analysed. A calculated sample size is a total of 280 participants (accounting for 8% drop-out), randomised in 1:1 fashion to 140 in the verum and 140 placebo group.</p><p><strong>Conclusion: </strong>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, to improve exercise tolerance and preclude the development of cardiac impairment.</p><p><strong>Clinical trial identifier: </strong>NCT05619653.</p>","PeriodicalId":15221,"journal":{"name":"Journal of Cardiovascular Magnetic Resonance","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design and Rationale of MYOFLAME-19 RCT: MYOcardial protection to reduce inFLAMmatory heart disease due to COVID-19 Infection using CMR Endpoints.\",\"authors\":\"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\",\"doi\":\"10.1016/j.jocmr.2024.101121\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute COVID-19 illness and without overt structural heart disease. Cardiac 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 prior to development of myocardial injury and impairment is missing.</p><p><strong>Trial design: </strong>Prospective multicentre randomised placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodelling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no preexisting significant comorbidities or structural heart disease, undergo standardised assessments with questionnaires, CMR imaging and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical Post-COVID inflammatory involvement on baseline CMR examination are randomised 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 (LVEF) to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at the 5% 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 analysed 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 analysed. A calculated sample size is a total of 280 participants (accounting for 8% drop-out), randomised in 1:1 fashion to 140 in the verum and 140 placebo group.</p><p><strong>Conclusion: </strong>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, to improve exercise tolerance and preclude the development of cardiac impairment.</p><p><strong>Clinical trial identifier: </strong>NCT05619653.</p>\",\"PeriodicalId\":15221,\"journal\":{\"name\":\"Journal of Cardiovascular Magnetic Resonance\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cardiovascular Magnetic Resonance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jocmr.2024.101121\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiovascular Magnetic Resonance","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jocmr.2024.101121","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Design and Rationale of MYOFLAME-19 RCT: MYOcardial protection to reduce inFLAMmatory heart disease due to COVID-19 Infection using CMR Endpoints.
Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute COVID-19 illness and without overt structural heart disease. Cardiac 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 prior to development of myocardial injury and impairment is missing.
Trial design: Prospective multicentre randomised placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodelling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no preexisting significant comorbidities or structural heart disease, undergo standardised assessments with questionnaires, CMR imaging and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical Post-COVID inflammatory involvement on baseline CMR examination are randomised 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 (LVEF) to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at the 5% 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 analysed 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 analysed. A calculated sample size is a total of 280 participants (accounting for 8% drop-out), randomised in 1:1 fashion to 140 in the verum and 140 placebo group.
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, to improve exercise tolerance and preclude the development of cardiac impairment.
期刊介绍:
Journal of Cardiovascular Magnetic Resonance (JCMR) publishes high-quality articles on all aspects of basic, translational and clinical research on the design, development, manufacture, and evaluation of cardiovascular magnetic resonance (CMR) methods applied to the cardiovascular system. Topical areas include, but are not limited to:
New applications of magnetic resonance to improve the diagnostic strategies, risk stratification, characterization and management of diseases affecting the cardiovascular system.
New methods to enhance or accelerate image acquisition and data analysis.
Results of multicenter, or larger single-center studies that provide insight into the utility of CMR.
Basic biological perceptions derived by CMR methods.