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

NCT04666454 | Recruiting Phase 4 DMC

• 1 other identifier: BROKEN SWEDEHEART
• Study Type: interventional
• Target: 1,000
• Locations: 3 countries
• Sites: 16

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.

Conditions

Takotsubo Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• 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)

Study Arms (4)

Randomisation 1: Adenosine and Dipyridamole

ACTIVE COMPARATOR

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.

Drug: Adenosine; Drug: Dipyridamole 200 mg

Randomisation 1: Control

OTHER

Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.

Other: Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome

Randomisation 2: Apixaban

ACTIVE COMPARATOR

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.

Drug: Apixaban 5 mg Oral Tablet

Randomisation 2: No anticoagulant therapy

NO INTERVENTION

Interventions

Adenosine DRUG

Adenosine infusion 70 µg/kg/min for 3 hours.

Randomisation 1: Adenosine and Dipyridamole

Dipyridamole 200 mg DRUG

200 mg b.i.d

Randomisation 1: Adenosine and Dipyridamole

Apixaban 5 mg Oral Tablet DRUG

5mg b.i.d

Randomisation 2: Apixaban

Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome OTHER

This treatment will vary depending on local routines and the degree of adherence to the recommendations.

Randomisation 1: Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Göteborg University: collaborator

Study Sites (16)

Aarhus Universitetshospital

Aarhus, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Östersund Sjukhus

Östersund, Jämtland Härjedalen, 831 27, Sweden

RECRUITING

Region Jönköpings Län

Jönköping, Region Jönköping, 55111, Sweden

RECRUITING

Norra Älvsborgs länssjukhus

Trollhättan, Västra Götalands Region, 46173, Sweden

RECRUITING

Region Dalarna

Falun, Sweden

RECRUITING

Sahlgrenska University Hospital, Department of Cardiology

Gothenburg, Sweden

RECRUITING

Skaraborg Hospital

Gothenburg, Sweden

RECRUITING

Region Skane Helsingborg Hospital

Helsingborg, Sweden

RECRUITING

Region Oestergoetland

Linköping, Sweden

RECRUITING

Region Skane - Skanes Universitetssjukhus

Lund, Sweden

RECRUITING

Region Orebro lan

Örebro, Sweden

RECRUITING

Danderyds Hospital, Department of Cardiology

Stockholm, Sweden

RECRUITING

Karolinska University Hospital, Huddinge, Department of Cardiology

Stockholm, Sweden

RECRUITING

Umeå University Hospital, Department of Cardiology

Umeå, Sweden

RECRUITING

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Takotsubo Cardiomyopathy

Interventions

Adenosine; Dipyridamole; apixaban; Tablets

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Elmir Omerovic, MD PhD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elmir Omerovic, MD PhD

CONTACT

31 3421000; elmir@wlab.gu.se

Björn Redfors, MD, PhD

CONTACT

31 3421000

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Multinational, Multicentre, registry-based, open-label, randomized controlled trial with 2 × 2 factorial design

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: December 14, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: To be decided
• Access Criteria: To be decided (TBD)

Locations

NO (1); SE (13); DK (2)