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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Takotsubo Syndrome
• Intervention / Treatment: Drug: Adenosine; Drug: Dipyridamole 200 mg; 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

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elmir Omerovic, MD PhD; Phone Number: +46 31 3421000; Email: elmir@wlab.gu.se
• Study Contact Backup: Name: Björn Redfors, MD, PhD; Phone Number: +46 31 3421000

Study Locations

• Denmark
  • Aarhus, Denmark
    • Recruiting
    • Aarhus Universitetshospital
    • Contact: Steen Hvitfeldt Poulsen, MD
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Contact: Lia Evi Bang, MD
• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Njord Nordstrand, MD
• Sweden
  • Falun, Sweden
    • Recruiting
    • Region Dalarna
    • Contact: Per Lundberg, MD
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital, Department of Cardiology
  • Gothenburg, Sweden
    • Recruiting
    • Skaraborg Hospital
    • Contact: Lisa Brandin, MD
  • Helsingborg, Sweden
    • Recruiting
    • Region Skane Helsingborg Hospital
    • Contact: Sven-Erik Olsson, MD
  • Linköping, Sweden
    • Recruiting
    • Region Oestergoetland
    • Contact: Joakim Alfredsson, MD
  • Lund, Sweden
    • Recruiting
    • Region Skane - Skanes Universitetssjukhus
    • Contact: Nazim Isma, MD
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital, Huddinge, Department of Cardiology
    • Contact: Loghman Henareh, MD
  • Stockholm, Sweden
    • Recruiting
    • Danderyds Hospital, Department of Cardiology
    • Contact: Christina Ekenbäck, MD
  • Umeå, Sweden
    • Recruiting
    • Umeå University Hospital, Department of Cardiology
    • Contact: Henrik Hagström, MD
  • Örebro, Sweden
    • Recruiting
    • Region Örebro Län
    • Contact: Anna Nordenskjöld, MD
  • Jämtland Härjedalen
    • Östersund, Jämtland Härjedalen, Sweden, 831 27
      • Recruiting
      • Östersund Sjukhus
      • Contact: Fredrik Björklund, MD; Phone Number: 063-14 75 00; Email: fredrik.bjorklund@regionjh.se
      • Principal Investigator: Fredrik Björklund, MD
  • Region Jönköping
    • Jönköping, Region Jönköping, Sweden, 55111
      • Recruiting
      • Region Jönköpings län
      • Contact: Dario Gulin, MD; Phone Number: 010-241 00 00; Email: dario.gulin@rjl.se
      • Principal Investigator: Dario Gulin, MD
  • Västra Götalands Region
    • Trollhättan, Västra Götalands Region, Sweden, 46173
      • Recruiting
      • Norra Älvsborgs Länssjukhus
      • Contact: Imran Tahir, MD; Phone Number: 010-435 00 00; Email: imran.tahir@vgregion.se
      • Principal Investigator: Imran Tahir, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Adenosine; Adenosine infusion 70 µg/kg/min for 3 hours.; Drug: Dipyridamole 200 mg; 200 mg b.i.d
Other: Randomisation 1: Control; 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; This treatment will vary depending on local routines and the degree of adherence to the recommendations.
Active Comparator: 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.	Drug: Apixaban 5 mg Oral Tablet; 5mg b.i.d
No Intervention: Randomisation 2: No anticoagulant therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: The Sahlgrenska Academy at University of Gothenburg
• Investigators: Principal Investigator: Elmir Omerovic, MD PhD, Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Estimated): December 2, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Cardiomyopathies; Ventricular Dysfunction; Ventricular Dysfunction, Left; Syndrome; Takotsubo Cardiomyopathy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Protease Inhibitors; Enzyme Inhibitors; Sensory System Agents; Analgesics; Neurotransmitter Agents; Anti-Arrhythmia Agents; Platelet Aggregation Inhibitors; Purinergic Agents; Vasodilator Agents; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Agonists; Purinergic Agonists; Apixaban; Adenosine; Dipyridamole
• Other Study ID Numbers: BROKEN SWEDEHEART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: To be decided.
• IPD Sharing Time Frame: To be decided
• IPD Sharing Access Criteria: To be decided (TBD)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No