Anakinra Versus Placebo Double Blind Randomized Controlled Trial for the Treatment of Acute MyocarditIS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Number of days alive free of any myocarditis complications
研究概览
简要总结
There is no specific treatment of acute myocarditis, especially during the inflammatory period. Interleukin (IL) is specifically involved during this period and play a role in myocardial oedema. ANAKINRA, an IL-1β Blocker, is a new treatment that has never been evaluated in myocarditis. The benefit for the patient could be important with a reduction of heart failure and ventricular arrhythmias.
Hypothesis : ANAKINRA in addition to standard therapy for treatment of Acute Myocarditis is superior to standard therapy based on an association of beta-blockers and Angiotensin-Converting-Enzyme inhibitor (ACE).
详细描述
It is a Double Blind Randomized clinical trial Phase IIb of superiority, enrolling two groups: one group treated with the standard of care, defined as the maximum tolerated dosage of any beta blockers and ACE, and placebo versus ANAKINRA in addition to the standard of care in patients treated for an acute Myocarditis.
Patients will be randomized to receive ANAKINRA 100 mg/daily or placebo subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months. Randomization 1:1 will be conducted centrally using the electronic Case Report Form (eCRF).
As an exploratory analysis, a second randomization for ACE discontinuation in patients without left ventricular dysfunction (LVEF > 50%) at one month post discharge will be performed.
One group will stopped the treatment at one month and the second group will continued the ACE for 6 months. This second randomization is in open label.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients hospitalized for Acute myocarditis defined as:
- •Chest Pain (or modification of the ECG) AND Troponin Rise (*1.5 Normal range) AND Myocarditis proven by MRI in the first 72h after admission
- •Age > 18 and <65 years old
- •Accepting effective contraception during treatment duration (men and women childbearing potential)
- •Signed informed consent Normal Coronary angiography or coronary CT Scan (made during the previous year is acceptable) (normal is defined as stenosis < 50%) (In the case of patients under 40 with typical MRI of myocarditis, coronary angiography is not mandatory and left to the doctor's discretion)
排除标准
- •Active coronary disease
- •Clinical Suspicion or proven underlying disease: systemic lupus, antiphospholipid antibodies, Lyme disease, trypanosomiase disease, myositis, signs of sarcoidosis, giant cell myocarditis, treated chronic inflammatory disease, tuberculosis, HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV), Hepatitis B virus (HBV) infection,
- •Latex allergy
- •Pregnancy, breastfeeding
- •Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients, neutropenia < 1,5.10^9/L)
- •Renal failure, Creatine Clearance (CrCl) < 30 ml/min (MDRD)
- •Malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study
- •History of malignancy
- •Non Steroidian Anti Inflammatory drug within the past 14 days
- •Anti Tumor Necrosis Factor (TNF) within the past 14 days
- •No affiliation to the French Health Care System "sécurité sociale"
- •Hepatic impairment = Child-Pugh Class C
- •Mechanical ventilation
- •Circulatory assistance
研究组 & 干预措施
A: ANAKINRA
ANAKINRA 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.
干预措施: ANAKINRA 100 mg/daily subcutaneously (Drug)
B: Placebo
PLACEBO 100 mg/daily subcutaneously once a day until hospital discharge, for a maximum of 14 days, in addition to standard care: ACE and Beta-blocker for 6 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of days alive free of any myocarditis complications
时间窗: within 28 days post hospitalization
Number of days alive free of any myocarditis complications defined as ventricular arrhythmias, heart failure, chest pain, ventricular dysfunction defined as LVEF\<50%, within 28 days post hospitalization
次要结局
- Total cost(on average 14 days)
- Total Quality Adjusted Life Year (QALYs),(on average 14 days)
- Ventricular tachycardia(during the 12 months follow-up)
- NT-proBNP above 450 pg/mL (in patients aged below 50); above 900 pg/mL (age 50-75 years) or BNP ≤ 400pg/mL 50% decrease of the troponin level at discharge compared to admission(an average of 14 days)
- Heart Failure(at 12 months)
- Left Ventricul Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE)(at 6 month)
- LVEF assessed by cardiac MRI(at 1 year)
- Incremental cost effectiveness(on average 14 days)
- Left Ventricul Ejection Fraction (LVEF) assessed by cardiac Magnetic Resonance Imaging (MRI)(at 6 month)
- All cause of death rate(during the 12 months follow-up)
- Cardiovascular death(at 12 months)
- Cost utility ratios(on average 14 days)
- LVEF assessed by cardiac TTE(at 1 year)