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

Phase 4

Recruiting

• Conditions: Takotsubo Syndrome
• Interventions: Other: Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome; Drug: Apixaban 5 mg Oral Tablet; Drug: Adenosine; Drug: Dipyridamole 200 mg

• Registration Number: NCT04666454
• Lead Sponsor: Vastra Gotaland Region

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-07
• Study First Submitted QC: 2020-12-07
• Study Start: 2020-12-14
• Study First Posted: 2020-12-14
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-12-02
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Randomisation 1: Adenosine and Dipyridamole	Dipyridamole 200 mg	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.
Randomisation 1: Control	Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome	Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.
Randomisation 2: Apixaban	Apixaban 5 mg Oral Tablet	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.
Randomisation 1: Adenosine and Dipyridamole	Adenosine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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: Presence of cardiac thrombus	at 48-96 hours
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)

Trial Locations

Locations (16)

Östersund Sjukhus; 🇸🇪 Östersund, Jämtland Härjedalen, Sweden

Region Jönköpings Län; 🇸🇪 Jönköping, Region Jönköping, Sweden

Norra Älvsborgs länssjukhus; 🇸🇪 Trollhättan, Västra Götalands Region, Sweden

Aarhus Universitetshospital; 🇩🇰 Aarhus, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Oslo University Hospital; 🇳🇴 Oslo, Norway

Region Dalarna; 🇸🇪 Falun, Sweden

Sahlgrenska University Hospital, Department of Cardiology; 🇸🇪 Gothenburg, Sweden

Skaraborg Hospital; 🇸🇪 Gothenburg, Sweden

Region Skane Helsingborg Hospital; 🇸🇪 Helsingborg, Sweden

Region Oestergoetland; 🇸🇪 Linköping, Sweden

Region Skane - Skanes Universitetssjukhus; 🇸🇪 Lund, Sweden

Danderyds Hospital, Department of Cardiology; 🇸🇪 Stockholm, Sweden

Karolinska University Hospital, Huddinge, Department of Cardiology; 🇸🇪 Stockholm, Sweden

Umeå University Hospital, Department of Cardiology; 🇸🇪 Umeå, Sweden

Region Orebro lan; 🇸🇪 Örebro, Sweden