Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy. (NCT04654988) | Clinical Trial Compass
RecruitingPhase 4
Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy.
Poland100 participantsStarted 2022-12-01
Plain-language summary
Myocarditis can result in numerous complications, but there is paucity of data regarding optimal therapy, short- and long-term effects of possibly effective immunosuppressive therapy. The IMPROVE-MC study will provide high-quality scientific data about efficacy and safety of immunosuppressive therapy, non-invasive (MRI, biomarkers) and invasive diagnostics tests (endomyocardial biopsy), and prognosis in myocarditis. The objective of this multicenter, prospective, randomized, double-blind placebo-controlled trial is to assess the efficacy and safety of 12 - month treatment with prednisone and azathioprine comparing to placebo on top of guideline-recommended medical therapy in patients with biopsy-proven virus negative myocarditis or inflammatory cardiomyopathy and reduced ejection fraction (LVEF ≤ 45%). The study will also assess persistence of the treatment effects after 12 months.
Who can participate
Age range18 Years – 65 Years
SexALL
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Inclusion criteria
✓. Written informed consent to participate in the IMPROVE-MC study (including two EMBs and two cardiac CMRs) prior to any evaluation or procedure related to the study.
✓. Patient with clinically suspected myocarditis or inflammatory cardiomyopathy (according to the criteria of the ESC Working Group on Myocardial \& Pericardial Diseases 2013 and ESC Heart Failure Guidelines 2021); OR/ AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy who will undergo diagnostic right ventricular (or/and left ventricular) EMB during the screening; OR / AND, Patients with already diagnosed active myocarditis (lymphocytic or eosinophilic) or inflammatory cardiomyopathy confirmed by right ventricular (or/and left ventricular) EMB that was performed according to the IMPROVE-MC study protocol within 3 months from screening.
✓. Men or women aged 18-65. Women of childbearing age must have a negative pregnancy test result. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (with a failure rate of \< 1% per year) for the duration of the study (from the time they sign consent) and for 8 weeks after the last dose of study treatment to prevent pregnancy. Patients agreeing to total sexual abstinence can also be included, assuming it is their usual lifestyle. Women are considered postmenopausal and without the potential to have a child if they have 12 months of natural (spontaneous) amenorrhea with an appropriate clinical picture (e.g. appropriate age, history of vasomotor symptoms) or have undergone bilateral surgical ovariectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of ovariectomy alone, only if the reproductive status of the woman has been confirmed by assessing hormone levels.
✓. No significant improvement in clinical condition or worsening course of the disease despite the standard treatment in the investigator's opinion, in the last ≥ 3 months prior to the screening period.
✓. LVEF 10 - 45% measured by echocardiogram taken during the screening period
✓. No significant LVEF improvement in the last ≥3 months prior to the screening period in the investigator's opinion.
✓. LVEF should be measured under stable conditions as assessed by the investigator.
✓. LVEF should be verified in the CORE-LAB.
Exclusion criteria
✕. Presence of contraindications to immunosuppressive therapy with steroids and/ or azathioprine (including hypersensitivity to azathioprine/ 6-mercaptopurine or prednisone, mainly untreated systemic infection, uncontrolled diabetes, poorly controlled endocrine diseases, osteoporosis, active gastric or duodenal ulcer, uncontrolled hypertension, leukocytopenia (leukocyte counts \<4 x 109/l), neutropenia (neutrophils \<1.5 x 109/l), thrombocytopenia (platelet levels \<130 x 109/l), anemia (hemoglobin levels \<11 g/dl).
✕. Positive clinical screening for active infections, including HIV, HBV, HCV. Assessment of tuberculosis infection should be considered before screening, according to the local epidemiologic status and according to investigator's opinion. After careful evaluation of the activity of the infection (or cure of the infection), the patient may continue participation in the study according to investigator's opinion.
✕. Another specific cause of heart failure (including severe congenital, valvular, hypertensive, and/or coronary artery disease) that could justify the severity of cardiac dysfunction.
✕. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), storage diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, genetic hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or known pericardial constriction.
✕. Diagnosed or suspected cardiac sarcoidosis or giant cell myocarditis, autoimmune/ systemic immune-mediated disease (i.e. granulomatosis with polyangiitis, lupus erythematosus) that might require specific immunosuppressive therapy. Recent, current or expected future need for long-term use of immunosuppressive therapy with steroids and/ or azathioprine and/ or other immunosuppressive agent (caution - short-term course of steroids \[i.e. for asthma attack, occasional topical applications\] is not an exclusion).
✕. NYHA class I and IV.
✕. Subjects with body mass index \>40 kg/m2 or body weight \<50 kg.
✕. Pregnancy, lactation or women who plan to become pregnant during the trial. Lack of consent to the use of effective forms of contraception.