BROKEN-SWEDEHEART- Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome. A Multinational, Multicentre, Registry-based, Open-label, Randomized Controlled Trial.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 16
- 主要终点
- Randomization 1: First co-primary endpoint: Wall motion score index (defined as the semi-quantitative score according to the American Society of Echocardiography)
研究概览
简要总结
The aim of this study is to document an optimized pharmacologic treatment for patients with Takotsubo Syndrome. There is currently no published documentation in a large number of patients. The study is a Randomized Registry Clinical Trial and in total 1000 patients registered in SWEDEHEART will be included.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
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.
- •A clinical diagnosis of TS (see definition 2.1), including an ejection fraction (EF) ˂ 50 % at baseline
- •Written informed consent obtained
排除标准
- •Previous randomization in the trial
- •Any concomitant condition resulting in a life expectancy of less than one month
- •Previously diagnosed left ventricular ejection fraction <50%
- •Known cardiomyopathy (except previous Takotsubo syndrome)
- •Known hemodynamically significant valve disease (moderate or severe aortic/mitral regurgitation) or stenosis
- •Heart transplant or left ventricular assist device recipient
- •Most recent (within the most recent 3 months) haemoglobin ˂10 g/dL
- •Systolic blood pressure <80 mm Hg at screening
- •Estimated glomerular filtration rate <30 mL/min/1.73m2
- •Current dialysis
- •Pregnancy or of childbearing potential who is not sterilized or is not using a medically accepted form of contraception
- •Not suitable in the opinion of the investigator due to severe or terminal comorbidity with poor prognosis, or characteristics that may interfere with adherence to the trial protocol
- •Specific exclusion criteria for Randomization 1
- •Any contra-indication for treatment with adenosine or dipyridamole (including AV-block II and III, sick-sinus syndrome in subjects who don´t have a functioning pacemaker, unstable angina, ongoing treatment with dipyridamole)
- •Severe asthma (defined as asthma requiring medium or high-dose inhaled corticosteroids combined with other long-acting medications) and severe Chronic Obstructive Pulmonary Disease (COPD), (defined as FEV-1 ˂ 50 %)
- •Ongoing treatment with dipyridamole
- •Declined participation in study 1
- •Specific exclusion criteria for Randomization 2
- •Any contra-indication for anticoagulant treatment.
- •Current indication for treatment with, anticoagulant or dual antiplatelet therapy
- •Declined participation in study 2
研究组 & 干预措施
Randomisation 1: Adenosine and Dipyridamole
Adenosine infusion 70 µg/kg/min for 3 hours, followed (first dose 60 minutes apart from the end of the adenosine infusion) by daily oral treatment with the adenosine reuptake inhibitor dipyridamole (200 mg b.i.d.) until normalization of Left Ventricular (LV) function (EF≥50%) is documented on the study-specific echocardiographic assessment at 48-96 hours or at any subsequent echocardiographic examination, or for 30+7 Days.
干预措施: Adenosine (Drug)
Randomisation 1: Adenosine and Dipyridamole
Adenosine infusion 70 µg/kg/min for 3 hours, followed (first dose 60 minutes apart from the end of the adenosine infusion) by daily oral treatment with the adenosine reuptake inhibitor dipyridamole (200 mg b.i.d.) until normalization of Left Ventricular (LV) function (EF≥50%) is documented on the study-specific echocardiographic assessment at 48-96 hours or at any subsequent echocardiographic examination, or for 30+7 Days.
干预措施: Dipyridamole 200 mg (Drug)
Randomisation 1: Control
Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.
干预措施: Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome (Other)
Randomisation 2: Apixaban
Apixaban 5mg b.i.d. per oral until normalization of LV function (EF≥50%) is documented on the study-specific echocardiographic assessment at 48-96 hours or any subsequent echocardiographic examination, or for 30+7 Days.
干预措施: Apixaban 5 mg Oral Tablet (Drug)
结局指标
主要结局
Randomization 1: First co-primary endpoint: Wall motion score index (defined as the semi-quantitative score according to the American Society of Echocardiography)
时间窗: 48-96 hours
Randomization 1: Second co-primary endpoint: The occurrence of the composite of death, cardiac arrest, or the need for cardiac mechanical assist device, or re-hospitalization for heart failure or ejection fraction <50%
时间窗: up until day 30 day respectively at 48-96 hours
Randomization 2: The occurrence of any thromboembolic event (defined as ischemic stroke, peripheral arterial embolization or myocardial infarction) or death, or the presence of a cardiac thrombus, as assessed by echocardiography
时间窗: up until day 30 respectively 48-96 hours
次要结局
- Randomization 2: Presence of cardiac thrombus(at 48-96 hours)
- Randomization 1: The hierarchical occurrence (in descending order of importance) of time to death, time to cardiac assist device, time to cardiac arrest and ejection fraction <50%(all time to the first occurrence up until day 30 respectively at 48-96 hours (binary))
- Randomization 1: Ejection fraction(at 48-96 hours (continuous))
- Randomization 1: Any sustained ventricular tachycardia or fibrillation(within 48-96 hours (binary))
- Randomization 1: Any high-grade atrioventricular block or sinus arrest(within 48-96 hours (binary))
- Randomization 1: Need for cardiac assist device(up until day 30 day (binary))
- Randomization 1: Death(up until day 30 (binary))
- Randomization 1: Stroke(up until day 30 (binary))
- Randomization 1: Worsening heart failure in hospital (defined as worsening signs or symptoms of heart failure, necessitating intensification of intravenous pharmacologic heart failure therapy or mechanical ventilation)(up until day 30)
- Randomization 2: Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria minor or major(up until day 30 (binary))
- Randomization 2: Bleeding Academic Research Consortium (BARC) grade 2-5(up until day 30 (binary))
- Randomization 2: BARC grade 3-5(up until day 30 (binary))
- Randomization 2: Any blood transfusion(up until day 30 (binary))