Beta-Blockers in Takotsubo Syndrome Study (β-Tako)

Beta-Blockers in Takotsubo Syndrome Study: A Randomized Clinical Trial (β-Tako)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Takotsubo Cardiomyopathy; Echocardiography; Left Ventricular Function; Beta-blockers
• Intervention / Treatment: Drug: Beta blocker

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fernando Alfonso, MD; Phone Number: 34 680483165; Email: falf@hotmail.com

Study Locations

• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
    • Contact: Fernando Alfonso, MD; Phone Number: 34 680483165; Email: falf@hotmail.com
    • Principal Investigator: Fernando Alfonso, MD
    • Principal Investigator: Jorge Salamanca, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beta-blockers; Beta-blockers with alpha or NO activity will be used. Dosage according to responsible physician and current clinical practice	Drug: Beta blocker; Pragmatic design. Any beta-blocker with alpha or NO activity may be used; Other Names: Other medications according to local clinical practice protocols and current guidelines
No Intervention: No beta-blockers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wall motion score index	Wall motion score index by echocardiography to assess recovery of left ventricular function Wall motion score index (WMSI) ranges from 1 to 4 (1 is normal and 4 worse)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction	Left ventricular ejection fraction by echocardiography to assess recovery of left ventricular function	7 days
Global longitudinal strain	Global longitudinal strain by echocardiography to assess recovery of left ventricular function	7 days
Delta (Change) in: wall motion score index, left ventricular ejection fraction, global longitudinal strain	Changes in LV function by imaging	7 days
Delta (Change) in: wall motion score index, left ventricular ejection fraction, global longitudinal strain	Changes in LV function by imaging	1 month
Combined clinical endpoint (death, stroke, recurrent TTS, heart failure, acute coronary syndrome, atrial fibrillation	Combined clinical endpoint	1 year
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	Individual clinical endpoints Occurrence of death, stroke, recurrent TT, heart failure, acute coronary syndrome, atrial fibrillation will be analyzed and compared individually in the 2 groups	1 year
Angina and quality of life status during daily life assessed in routine clinical practice	Evaluated in clinical visits	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Magnetic Resonance (CMR)	CMR to detect edema, late gadolinium enhancement to correlate with clinical data and prognosis	1 year
Coronary angiography	To assess correlation with angiographic features and clinical findings and prognosis	1 year
Biomarkers, inflammatory data, mRNAs	Association with clinical findings and prognosis	1 year
ECG	Correlation of ECG findings with clinical features and prognosis Different ECG parameters will be correlated with the echocardiographic and clinical outcome measures to detect potential correlations	1 year
Pharmacogenetic substudy	To assess pharmacogenetic implications of different beta-blockers used The pharcacogenetics of the 2 different betablockers used in this study will be studied in relation to the main echocardiographic and clinical endpoints	1 year

Collaborators and Investigators

• Sponsor: Spanish Society of Cardiology
• Collaborators: Hospital Universitario de La Princesa (Madrid, Spain)
• Investigators: Study Chair: Fernando Alfonso, MD, Hospital Universitario La Princesa, Madrid. IIS-IP

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 8, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Heart failure; acute coronary syndrome; echocardiography; stress; left ventricular function; acute myocardial infarction; coronary angiography; beta-blockers; Takotsubo Cardiomyopathy; Normal coronary arteries
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Cardiomyopathies; Takotsubo Cardiomyopathy; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-Antagonists
• Other Study ID Numbers: 10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be considered to be shared by the PI and steering committee, upon adequate and justified request, within a defined scientific research project, and providing adequate supervision of the analysis and credit to the original inverstigators is prearranged
• IPD Sharing Time Frame: 1 year after publication of the main combined clinical endpoint
• IPD Sharing Access Criteria: to be defined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; 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