A Multicenter, Randomized, Double-blind, Placebo-controlled TRial Evaluating Immunosuppressive Treatment in Patients With Chronic Virus-Negative Inflammatory cardiomyopaThY (TRINITY Trial)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 14
- 主要终点
- LVEF increase (metric)
研究概览
简要总结
Evaluating Immunosuppressive treatment (Mycophenolate mofetil and prednisolon compared to placebo) for 6 months in patients with chronic virus- Negative Inflammatory cardiomyopathy - a multicenter, randomized, double-blind, placebo-controlled trial.
详细描述
Inflammatory cardiomyopathy constitutes a relevant part of the cohort of non-dilated left ventricular cardiomyopathy / dilated cardiomyopathy (DCM) and is associated with adverse outcome. Urgent medical needs remain with respect to the therapeutic options for inflammatory cardiomyopathy. So far, no specific therapy for patients with inflammatory cardiomyopathy is available. Existing data on immunosuppression for inflammatory cardiomyopathy is preliminary and needs further validation by larger randomized, controlled, multicenter trials.
Patients with biopsy-proven virus-negative inflammatory dilated or non-dilated left ventricular cardiomyopathy and moderate to severe deterioration of cardiac function despite optimal medical treatment (OMT) for heart failure (HF) will be randomized (1:1) in a double-blinded way to Mycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime for 6 months or placebo. The clinical benefit will be measured with respect to absolute increase in LVEF (metric and binary co-primary endpoints assessed by MRI core lab) of immunosuppressive treatment with MMF and prednisolone compared to placebo at 12 months follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Medical therapy for HF for ≥3 months and <10 years according to current guideline recommendations
- •Persistent reduction of LVEF <50% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion
- •EMB with immunohistochemical evidence of lymphocytic myocarditis defined as ≥14 leukocytes/mm2 including up to 4 monocytes/mm2 with the presence of CD3 positive T-lymphocytes ≥7 cells/mm2 and increased MHC-II expression as approved by the histopathology core lab
- •Absence of established cardiotropic virus infection in EMBs (i.e. enteroviruses, HHV-6, EBV, CMV, adenoviruses, parvovirus B19 >500 copies) as approved by the histopathology core lab
- •Negative pregnancy test and the use of a highly effective contraceptive measure in women with child-bearing potential (according to CTFG recommendations)
- •Written informed consent.
排除标准
- •Histopathological (as approved by the histopathology core lab) and/ or clinical evidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilic myocarditis,
- •Known systemic inflammatory disease,
- •Recent major surgery within <6 weeks, recent ICD implantation within <6 weeks or recent CRT implantation within <3 months prior to,
- •Known coronary artery disease responsible for cardiac dysfunction (i.e., prior myocardial infarction, persistent stenosis ≥ 70%),
- •Pregnancy or lactation,
- •Contraindications to immunosuppressive treatment with MMF + corticosteroids,
- •Inability to provide informed consent.
研究组 & 干预措施
Immunosuppressive treatment
Mycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime
干预措施: Mycophenolate Mofetil (Drug)
Immunosuppressive treatment
Mycophenolate mofetil (MMF) 1g bid and prednisolone at initially 1mg/kg in a step-down regime
干预措施: Prednisolone (Drug)
Placebo
Mycophenolate mofetil (MMF) and prednisolone Placebo
干预措施: Mycophenolate Mofetil Placebo (Drug)
Placebo
Mycophenolate mofetil (MMF) and prednisolone Placebo
干预措施: Prednisolone Placebo (Drug)
结局指标
主要结局
LVEF increase (metric)
时间窗: 12 months follow-up
Absolute increase in LVEF at 12 months follow-up as assessed by blinded investigators of the MRI core lab (metric endpoint)lab) of immunosuppressive treatment with MMF and prednisolone compared to placebo
LVEF increase (binary)
时间窗: 12 months follow-up
Proportion of patients with an absolute increase in LVEF ≥10% at 12 months follow-up as assessed by blinded investigators of the MRI core lab (binary endpoint).
次要结局
- LVEF increase 6 months (MRI)(6 months follow-up)
- Ventricular remodelling (MRI)(6 and 12 months follow-up)
- Strain (MRI)(6 and 12 months follow-up)
- Composite clinical outcome(12 months)
- LVEF increase (echo)(6 and 12 months follow-up)
- Ventricular remodelling (echo)(6 and 12 months follow-up)
- Strain (echo)(6 and 12 months follow-up)
- Diastolic parameters (echo)(6 and 12 months follow-up)
- Mitral and tricuspid regurgitation (echo)(6 and 12 months follow-up)
- Cardiopulmonary exercise capacity(6 and 12 months follow-up)
- NYHA(6 and 12 months follow-up)
- QoL(12 months)
- Cardiac autonomic function(6 and 12 months follow-up)
- Composite safety outcome(12 months)
- Biomarker(12 months)
研究者
Steffen Massberg
Prof. Dr. med.
LMU Klinikum