E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The medical condition is acute heart failure (Takotsubo syndrome) |
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E.1.1.1 | Medical condition in easily understood language |
The medical condition is acute heart failure (Takotsubo syndrome) which is an acute heart failure syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Objective for randomization 1: To investigate whether treatment with adenosine and dipyridamole improves clinical outcomes in Takotsubo Syndrome compared to standard care according to current recommendations from ESC taskforce for Takotsubo Syndrome |
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E.2.2 | Secondary objectives of the trial |
To investigate whether treatment with apixaban reduces the risk of thromboembolic events compared to no treatment with antithrombotic drugs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A clinical diagnosis of Takotsubo syndrome Age above 18 years Written informed consent |
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E.4 | Principal exclusion criteria |
Any contra indication for treatment with adenosine or dipyridamole Ongoing treatment with dipyridamole Life expectancy of less than one month |
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E.5 End points |
E.5.1 | Primary end point(s) |
Factorial design including randomization 1 and randomization 2: Randomization 1 First co-primary endpoint: Wall motion score index at 48-96 hours (defined as the semi-quantitative score according to the American Society of Echocardiography). Second primary endpoint: The occurance of the composite of death, cardiac arrest, or the need for cardiac mechanical assist device up until day 30, or ejaction fraction less than 50% at 48-96 hors post-randomization up until day 30, or re-hospitalisation up until day 30. Randomization 2 The occurance of any thromboembolic event (defined as ischemic stroke, peripheral arterial embolization or myocardial infarction) or death within 30 days or the presence of a cardiac thrombus at48-96 hours as assessed by echocardiography
1. The occurance of the composite of death, cardiac arrest (defined as ventricular fibrillation or asystole more than 30 seconds), or need for cardiac mechanical assist device within 30 days, or ejaction fraction lower than 50 % at 72 hours or rehospitalization for heart failure within 30 days
2. The occurance of any thromboembolic event (ischemic stroke, peripheral arterial embolization or myocardial infarction) or death within 30 days, or the presence of a cardiac thrombos at 72 hours, as assessed by echocardiography
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At day 30 and 48-96 hours post randomization |
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E.5.2 | Secondary end point(s) |
Randomization 1 The hierarchial occurance of time to death, time to cardiac assist device, time to cardiac arrest and ejaction fraction lower than 50 % within day 30 and ejaction fraction lower than 50% at 48-96 hours (binary) Other secondary endpoints: 1. Ejaction fraction at 48-96 (continous) 2. Any sustained ventricular tachycardia or fibrillation within 48-96 hours (binary) 3. Any high-grade atrioventricular block or sinus arrest within 48-96 hours (binary) 4. Need for cardiac assist device up until day 30 (binary) 5. Death up until day 30 6. Stroke up until day 30 7. The following outcomes at 6 months and 1-10 years - re-hospitalization for TS - all cause mortality 8. Worsening heart failure (defined as worsening signs or symptoms of heart failure necessitating intensification of intravenous pharmacologic heart failure therapy) Randomization 2 1.Presence of cardiac thrombus at 48-96 hours 2. Thrombolysis in Myocardial infarction (TIMI) bleeding criteria minor of major up until day 30 3. Bleeding Academic Research Consortium (BARC) grade 2-5 up until day 30 4. BARC grade 3-5 up until day 30 5. Any blood transfusion |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up until day 30 48-96 hours (relevant only for "ejaction fraction" |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
It is a registry-based R-RCT with factorial design (2x2) including 2 separate studies |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard clinical practice according to recommendations from ESC taskforce |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS is not the end of collecting endpoints. Day 30 is however the last visit in the study for this specific application. Data will also be taken from the SWEDEHEART during several years (up to 10 years) |
Primary endpoint will be evaluated at day 30 (last visit). Secondary endpoints will be evaluated at day 30, at 6 months and 12 months. After this patients will be followed up yearly for in total 10 years within the SWEDEHEART registry |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |