Clinical trial NCT04666454: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Takotsubo Syndrome
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Göteborg University
First posted: 2020-12-14
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Multinational, Multicentre, registry-based, open-label, randomized controlled trial with 2 × 2 factorial design
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Previous randomization in the trial
2. Any concomitant condition resulting in a life expectancy of less than one month
3. Previously diagnosed left ventricular ejection fraction \<50%
4. Known cardiomyopathy (except previous Takotsubo syndrome)
5. Known hemodynamically significant valve disease (moderate or severe aortic/mitral regurgitation) or stenosis
6. Heart transplant or left ventricular assist device recipient
7. Most recent (within the most recent 3 months) haemoglobin ˂10 g/dL
8. Systolic blood pressure \<80 mm Hg at screening
9. Estimated glomerular filtration rate \<30 mL/min/1.73m2
10. Current dialysis
11. Pregnancy or of childbearing potential who is not sterilized or is not using a medically accepted form of contraception
12. 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
13. 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)
14. 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 %)
15. Ongoing treatment with dipyridamole
16. Declined participation in study 1

Specific exclusion criteria for Randomization 2

1. Any contra-indication for anticoagulant treatment.
2. Current indication for treatment with, anticoagulant or dual antiplatelet therapy
3. Declined participation in study 2

Primary outcomes:
measure: Randomization 1: First co-primary endpoint: Wall motion score index (defined as the semi-quantitative score according to the American Society of Echocardiography)
timeFrame: 48-96 hours
measure: 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%
timeFrame: up until day 30 day respectively at 48-96 hours
measure: 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
timeFrame: up until day 30 respectively 48-96 hours
Secondary outcomes:
measure: 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%
timeFrame: all time to the first occurrence up until day 30 respectively at 48-96 hours (binary)
measure: Randomization 1: Ejection fraction
timeFrame: at 48-96 hours (continuous)
measure: Randomization 1: Any sustained ventricular tachycardia or fibrillation
timeFrame: within 48-96 hours (binary)
measure: Randomization 1: Any high-grade atrioventricular block or sinus arrest
timeFrame: within 48-96 hours (binary)
measure: Randomization 1: Need for cardiac assist device
timeFrame: up until day 30 day (binary)
measure: Randomization 1: Death
timeFrame: up until day 30 (binary)
measure: Randomization 1: Stroke
timeFrame: up until day 30 (binary)
measure: 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)
timeFrame: up until day 30
measure: Randomization 2: Presence of cardiac thrombus
timeFrame: at 48-96 hours
measure: Randomization 2: Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria minor or major
timeFrame: up until day 30 (binary)
measure: Randomization 2: Bleeding Academic Research Consortium (BARC) grade 2-5
timeFrame: up until day 30 (binary)
measure: Randomization 2: BARC grade 3-5
timeFrame: up until day 30 (binary)
measure: Randomization 2: Any blood transfusion
timeFrame: up until day 30 (binary)
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Östersund
country: Sweden
facility: Östersund Sjukhus
state: Jämtland Härjedalen
city: Jönköping
country: Sweden
facility: Region Jönköpings Län
state: Region Jönköping
city: Trollhättan
country: Sweden
facility: Norra Älvsborgs länssjukhus
state: Västra Götalands Region
city: Falun
country: Sweden
facility: Region Dalarna
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital, Department of Cardiology
city: Gothenburg
country: Sweden
facility: Skaraborg Hospital
city: Helsingborg
country: Sweden
facility: Region Skane Helsingborg Hospital
city: Linköping
country: Sweden
facility: Region Oestergoetland
city: Lund
country: Sweden
facility: Region Skane - Skanes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Danderyds Hospital, Department of Cardiology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Huddinge, Department of Cardiology
city: Umeå
country: Sweden
facility: Umeå University Hospital, Department of Cardiology
city: Örebro
country: Sweden
facility: Region Orebro lan
Study officials:
affiliation: Sahlgrenska University Hospital
name: Elmir Omerovic, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: