Clinical trial NCT06509074: Beta-Blockers in Takotsubo Syndrome Study
Official title: Beta-Blockers in Takotsubo Syndrome Study: A Randomized Clinical Trial (β-Tako)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Takotsubo Cardiomyopathy
Beta-blockers
Echocardiography
Left Ventricular Function
Keywords: Takotsubo Cardiomyopathy
beta-blockers
echocardiography
left ventricular function
acute myocardial infarction
acute coronary syndrome
coronary angiography
Normal coronary arteries
Heart failure
stress
Lead sponsor: Spanish Society of Cardiology
Sponsor class: OTHER
Collaborators: name: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
First posted: 2024-07-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized trial with 2 arms
Primary purpose: TREATMENT

Brief summary: The Beta-blockers in Takotsubo syndrome (TTS) (β-Tako) trial, is an academic, pragmatic, prospective, multicenter randomized clinical trial, aiming to assess the efficacy of beta-blockers (BB) in TTS patients. Two-hundred patients with TTS will be randomized (1:1) to BB (n=100) or no BB (n=100). BB with alpha or nitric oxide release activity will be used in the treatment arm. The primary endpoint will be the comparison of the wall motion score index by echocardiography at 7 days. A composite clinical endpoint (death, stroke, admission for recurrent TTS, ACS, heart failure or atrial fibrillation) at 1 year, will be assessed by an independent clinical events committee. Several sub-studies will be performed. The β-Tako trial will inform treatment decisions in this uniquely challenging clinical entity.

Detailed description: Takotsubo syndrome (TTS) is a cardiac condition mimicking acute coronary syndrome (ACS), characterized by transient left ventricular (LV) dysfunction in the presence of normal coronary arteries. Its etiology remains unknown but reversible microvascular dysfunction secondary to an adrenergic surge appears implicated. Treatment is empiric although in clinical practice most patients receive beta-blockers (BB). The Beta-blockers in TTS (β-Tako) trial, is an academic, pragmatic, prospective, multicenter randomized clinical trial, aiming to assess the efficacy of BB in TTS patients. TTS diagnosis will be confirmed by invasive coronary angiography and serial echocardiographic studies. Two-hundred patients with TTS will be randomized (1:1) to BB (n=100) or no BB (n=100). BB with alpha or nitric oxide release activity will be used in the treatment arm. The primary endpoint will be the comparison of the wall motion score index by echocardiography at 7 days, analyzed in an independent corelab. Changes in LV ejection fraction and global longitudinal strain will be also evaluated. A composite clinical endpoint (death, stroke, admission for recurrent TTS, ACS, heart failure or atrial fibrillation) at 1 year, will be assessed by an independent clinical events committee. Several sub-studies (clinical, imaging, biomarkers, pharmacogenetic, mRNAs, quality of life) will be performed. The β-Tako trial will generate valuable scientific evidence to address unmet clinical needs and inform clinical and treatment decisions in this uniquely challenging clinical entity.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Diagnosis of TTS with exclusion of significant coronary artery disease (CAD) by invasive coronary angiography

Exclusion Criteria:

* Patients diagnosed of TTS \> 48 hours before.
* Persistent ccardiogenic shock or severe hemodynamic instability
* Persistent severe (\>30 mmHg) intraventricular gradient
* Previous diagnosis of severe valvular or ventricular disease or prior myocardial infarction secondary to atherosclerotic CAD
* Patients already receiving treatment with betablockers (\*)
* Absolute contraindication/indication for beta-blockers (\*\*)
* Poor echocardiographic window
* Pregnant or breastfeeding women.
* Participation in another clinical trial.

(\*) Betablockers at a therapeutic dose at the time of symptom´s onset. (\*\*) Close ECG monitoring required in patients with hypotension, bradycardia or cQT interval prolongation

Primary outcomes:
measure: Wall motion score index
timeFrame: 7 days
Secondary outcomes:
measure: Left ventricular ejection fraction
timeFrame: 7 days
measure: Global longitudinal strain
timeFrame: 7 days
measure: Delta (Change) in: wall motion score index, left ventricular ejection fraction, global longitudinal strain
timeFrame: 7 days
measure: Delta (Change) in: wall motion score index, left ventricular ejection fraction, global longitudinal strain
timeFrame: 1 month
measure: Combined clinical endpoint (death, stroke, recurrent TTS, heart failure, acute coronary syndrome, atrial fibrillation
timeFrame: 1 year
measure: Individual endpoints of the combined clinical endpoint Occurrence of death, stroke, recurrent TT, heart failure, acute coronary syndrome, atrial fibrillation will be analyzed and compared individually
timeFrame: 1 year
measure: Angina and quality of life status during daily life assessed in routine clinical practice
timeFrame: 1 year
Other outcomes:
measure: Cardiac Magnetic Resonance (CMR)
timeFrame: 1 year
measure: ECG
timeFrame: 1 year
measure: Pharmacogenetic substudy
timeFrame: 1 year
measure: Coronary angiography
timeFrame: 1 year
measure: Biomarkers, inflammatory data, mRNAs
timeFrame: 1 year
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
Study officials:
affiliation: Hospital Universitario La Princesa, Madrid. IIS-IP
name: Fernando Alfonso, MD
role: STUDY_CHAIR
References: