Back to resultsBROKEN-SWEDEHEART-Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome
Primary Purpose
Takotsubo Syndrome
Status
Recruiting
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Adenosine
Dipyridamole 200 mg
Apixaban 5 mg Oral Tablet
Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome
Sponsored by
About this trial
This is an interventional treatment trial for Takotsubo Syndrome
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years.
- A clinical diagnosis of Takotsubo syndrome (TS)
- Written informed consent obtained
Exclusion Criteria:
- Previous randomization in the study
- Any contra-indication for treatment with adenosine or dipyridamole (including AV-block II and III, sick sinus syndrome in patients who do not have a functioning pacemaker, unstable angina, ongoing treatment with dipyridamole)
- Any concomitant condition resulting in a life expectancy of less than one month
- Previous myocardial infarction
- Previously diagnosed left ventricular ejection fraction <50%
- Known cardiomyopathy
- 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 <100 g/L
- 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 study-protocol
Specific subject exclusion criteria (Randomization 2)
- Any contra-indication for anticoagulant treatment.
- Current indication for treatment with, anticoagulant or dual antiplatelet therapy.
Sites / Locations
- Sahlgrenska University Hospital, Department of CardiologyRecruiting
- Danderyds Hospital, Department of Cardiology
- Karolinska University Hospital, Huddinge, Department of CardiologyRecruiting
- Umeå University Hospital, Department of Cardiology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Other
Active Comparator
No Intervention
Arm Label
Randomisation 1: Adenosine and Dipyridamole
Randomisation 1: Control
Randomisation 2: Apixaban
Randomisation 2: No anticoagulant therapy
Arm Description
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.
Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.
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.
Outcomes
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)
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%
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
Secondary Outcome Measures
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%
Randomization 1: Ejection fraction
Randomization 1: Any sustained ventricular tachycardia or fibrillation
Randomization 1: Any high-grade atrioventricular block or sinus arrest
Randomization 1: Need for cardiac assist device
Randomization 1: Death
Randomization 1: Stroke
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)
Randomization 2: Presence of cardiac thrombus
Randomization 2: Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria minor or major
Randomization 2: Bleeding Academic Research Consortium (BARC) grade 2-5
Randomization 2: BARC grade 3-5
Randomization 2: Any blood transfusion
Full Information
NCT ID
NCT04666454
First Posted
December 7, 2020
Last Updated
May 2, 2023
Sponsor
Vastra Gotaland Region
Collaborators
Sahlgrenska University Hospital, Sweden
1. Study Identification
Unique Protocol Identification Number
NCT04666454
Brief Title
BROKEN-SWEDEHEART-Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome
Official Title
Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2020 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vastra Gotaland Region
Collaborators
Sahlgrenska University Hospital, Sweden
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Takotsubo Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Model Description
Multicentre, registry-based, open-label, randomized controlled trial with 2 × 2 factorial design
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Randomisation 1: Adenosine and Dipyridamole
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Randomisation 1: Control
Arm Type
Other
Arm Description
Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.
Arm Title
Randomisation 2: Apixaban
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Randomisation 2: No anticoagulant therapy
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Adenosine
Intervention Description
Adenosine infusion 70 µg/kg/min for 3 hours.
Intervention Type
Drug
Intervention Name(s)
Dipyridamole 200 mg
Intervention Description
200 mg b.i.d
Intervention Type
Drug
Intervention Name(s)
Apixaban 5 mg Oral Tablet
Intervention Description
5mg b.i.d
Intervention Type
Other
Intervention Name(s)
Care as recommended by the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology for takotsubo syndrome
Intervention Description
This treatment will vary depending on local routines and the degree of adherence to the recommendations.
Primary Outcome Measure Information:
Title
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
Title
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
Title
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 Measure Information:
Title
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)
Title
Randomization 1: Ejection fraction
Time Frame
at 48-96 hours (continuous)
Title
Randomization 1: Any sustained ventricular tachycardia or fibrillation
Time Frame
within 48-96 hours (binary)
Title
Randomization 1: Any high-grade atrioventricular block or sinus arrest
Time Frame
within 48-96 hours (binary)
Title
Randomization 1: Need for cardiac assist device
Time Frame
up until day 30 day (binary)
Title
Randomization 1: Death
Time Frame
up until day 30 (binary)
Title
Randomization 1: Stroke
Time Frame
up until day 30 (binary)
Title
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
Title
Randomization 2: Presence of cardiac thrombus
Time Frame
at 48-96 hours
Title
Randomization 2: Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria minor or major
Time Frame
up until day 30 (binary)
Title
Randomization 2: Bleeding Academic Research Consortium (BARC) grade 2-5
Time Frame
up until day 30 (binary)
Title
Randomization 2: BARC grade 3-5
Time Frame
up until day 30 (binary)
Title
Randomization 2: Any blood transfusion
Time Frame
up until day 30 (binary)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years.
A clinical diagnosis of Takotsubo syndrome (TS)
Written informed consent obtained
Exclusion Criteria:
Previous randomization in the study
Any contra-indication for treatment with adenosine or dipyridamole (including AV-block II and III, sick sinus syndrome in patients who do not have a functioning pacemaker, unstable angina, ongoing treatment with dipyridamole)
Any concomitant condition resulting in a life expectancy of less than one month
Previous myocardial infarction
Previously diagnosed left ventricular ejection fraction <50%
Known cardiomyopathy
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 <100 g/L
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 study-protocol
Specific subject exclusion criteria (Randomization 2)
Any contra-indication for anticoagulant treatment.
Current indication for treatment with, anticoagulant or dual antiplatelet therapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elmir Omerovic, MD PhD
Phone
31 3421000
Ext
+46
Email
elmir@wlab.gu.se
First Name & Middle Initial & Last Name or Official Title & Degree
Björn Redfors, MD, PhD
Phone
31 3421000
Ext
+46
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elmir Omerovic, MD PhD
Organizational Affiliation
Sahlgrenska University Hospital, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sahlgrenska University Hospital, Department of Cardiology
City
Gothenburg
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Danderyds Hospital, Department of Cardiology
City
Stockholm
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Name
Karolinska University Hospital, Huddinge, Department of Cardiology
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Name
Umeå University Hospital, Department of Cardiology
City
Umeå
Country
Sweden
Individual Site Status
Not yet recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
To be decided.
IPD Sharing Time Frame
To be decided
IPD Sharing Access Criteria
To be decided (TBD)
Learn more about this trial
BROKEN-SWEDEHEART-Optimized Pharmacological Treatment for Broken Heart (Takotsubo) Syndrome
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