BROKEN-SWEDEHEART- Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome.

Official title

BROKEN-SWEDEHEART- Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome. A Multinational, Multicentre, Registry-based, Open-label, Randomized Controlled Trial.

Overview

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.

Interventions

• Drug Adenosine
  Adenosine infusion 70 µg/kg/min for 3 hours.
• Drug Dipyridamole 200 mg
  200 mg b.i.d
• Drug Apixaban 5 mg Oral Tablet
  5mg b.i.d
• Other Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome
  This treatment will vary depending on local routines and the degree of adherence to the recommendations.

Primary outcome measures

• Randomization 1: First co-primary endpoint: Wall motion score index (defined as the semi-quantitative score according to the American Society of Echocardiography) [Time frame: 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% [Time frame: 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 [Time frame: up until day 30 respectively 48-96 hours]

Secondary outcome measures (12)

• 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% [Time frame: all time to the first occurrence up until day 30 respectively at 48-96 hours (binary)]
• Randomization 1: Ejection fraction [Time frame: at 48-96 hours (continuous)]
• Randomization 1: Any sustained ventricular tachycardia or fibrillation [Time frame: within 48-96 hours (binary)]
• Randomization 1: Any high-grade atrioventricular block or sinus arrest [Time frame: within 48-96 hours (binary)]
• Randomization 1: Need for cardiac assist device [Time frame: up until day 30 day (binary)]
• Randomization 1: Death [Time frame: up until day 30 (binary)]
• Randomization 1: Stroke [Time frame: 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) [Time frame: up until day 30]
• Randomization 2: Presence of cardiac thrombus [Time frame: at 48-96 hours]
• Randomization 2: Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria minor or major [Time frame: up until day 30 (binary)]
• Randomization 2: Bleeding Academic Research Consortium (BARC) grade 2-5 [Time frame: up until day 30 (binary)]
• Randomization 2: BARC grade 3-5 [Time frame: up until day 30 (binary)]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years.
• A clinical diagnosis of TS (see definition 2.1), including an ejection fraction (EF) ˂ 50 % at baseline
• Written informed consent obtained

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 13 centers

• Östersund Sjukhus — Östersund
• Region Jönköpings Län — Jönköping
• Norra Älvsborgs länssjukhus — Trollhättan
• Region Dalarna — Falun
• Sahlgrenska University Hospital, Department of Cardiology — Gothenburg
• Skaraborg Hospital — Gothenburg
• Region Skane Helsingborg Hospital — Helsingborg
• Region Oestergoetland — Linköping
• … and 5 more centers

Denmark · 2 centers

• Aarhus Universitetshospital — Aarhus
• Rigshospitalet — Copenhagen

Norway · 1 center

• Oslo University Hospital — Oslo

Publications

• Omerovic E, James S, Erlinge D, Hagstrom H, Venetsanos D, Henareh L, Ekenback C, Alfredsson J, Hambreus K, Redfors B. Rationale and design of BROKEN-SWEDEHEART: a registry-based, randomized, parallel, open-label multicenter trial to test pharmacological treatments for broken heart (takotsubo) syndrome. Am Heart J. 2023 Mar;257:33-40. doi: 10.1016/j.ahj.2022.11.010. Epub 2022 Nov 23. PMID 36435233

Identifiers

NCT: NCT04666454 · BROKEN SWEDEHEART

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗