Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
200
Countries
1
Sites
27
Takotsubo Syndrome (TT) is an acute cardiac condition
To evaluate the clinical efficacy of the most widely used pharmacological therapeutic strategy in patients with Takotsubo Syndrome (TT) in clinical practice. Namely, to assess the role of beta-blockers with alpha activity or nitric oxide liberation, to facilitate left ventricular function recovery on echocardiography i…
Key facts
- Sponsor
- Fundacion Casa Del Corazon
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 8 Jul 2024 → ongoing
- Decision date (initial)
- 2024-03-25
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Fundación casa del corazón (Spanish Society of Cardiology -SEC)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
To evaluate the clinical efficacy of the most widely used pharmacological therapeutic strategy in patients with Takotsubo Syndrome (TT) in clinical practice. Namely, to assess the role of beta-blockers with alpha activity or nitric oxide liberation, to facilitate left ventricular function recovery on echocardiography in TT patients. The consistency of the treatment effect will be examined among several predefined relevant clinical subgroups after adjusting for multiple comparisons.
Secondary objectives 1
- Several secondary objectives will be also addressed using well-defined predefined ancillary studies. The main prospective systematic sub-studies include: 1) Assessment of other relevant echocardiographic outcome measures of left ventricular function (LVEF, GLS) at different time points after the index event, 2) Coronary angiographic assessment (visual and QCA), 3) Magnetic resonance imaging (MRI), 4) Intracoronary imaging (optical coherence tomography [OCT] and intravascular ultrasound [IVUS], 5) Invasive and noninvasive coronary physiological indexes, 6) Cardiac CT, 6), 7) Pharmacogenetics, 8) Inflammatory, immunologic, genetic and micro-RNA analyses, and 9) Quality of life (QoL) analyses (using classical, well accepted, questionnaires).
Conditions and MedDRA coding
Takotsubo Syndrome (TT) is an acute cardiac condition
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10066332 | Acute cardiac insufficiency | 10007541 |
| 20.1 | LLT | 10067676 | Takotsubo syndrome | 10007541 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | 6.7. Randomization, Intervention Eligible patients meeting the inclusion criteria and without any exclusion criteria will be randomized (ideally within 24 hours of diagnosis) after providing signed informed consent. Randomization (1:1) will be centrally performed using a computer-generated code. When required (doubtful cases) the coronary and left ventricular angiograms, echocardiograms (including additional imaging modalities as required) will be immediately reviewed online (at the time the patient is considered for inclusion) by experts on TT at the centralized corelab (Hospital Universitario de La Princesa in Madrid). This will be accomplished using an app already developed by our group for the currently ongoing BA-SCAD trial (50) preserving all the legal requirements for anonymization and data protection. Randomization will be performed in a blinded manner with the use of a computerized algorithm, with stratification according to site. The randomization system will be readily accessible online 24/7/365.
Interventions outside routine clinical practice will be minimized to follow the pragmatic design of the study.
|
Randomised Controlled | Single | [{"id":105997,"code":4,"name":"Analyst"},{"id":105996,"code":2,"name":"Investigator"}] |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-510213-25-00 | Beta-Blockers in Takotsubo Syndrome: A Randomized Clinical Trial | Fundacion Casa Del Corazon |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- • Written informed consent. • Diagnosis of TT (+) with exclusion of significant culprit coronary artery disease by invasive angiography (++)
Exclusion criteria 1
- • Patients diagnosed of TT > 48 hours before. • Persistent cardiogenic 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 beta-blockers (*) • Absolute contraindication/indication for beta-blockers (**) • Poor echocardiographic window • Pregnant or breastfeeding women. • Participation in another clinical trial.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Comparison of left ventricular systolic function recovery as assessed by the echocardiographic left ventricular wall motion score index (WMSI) at 7 days.
Secondary endpoints 1
- A) Changes in left ventricular function by other methods (LVEF and GLS). B) Comparison of clinical outcomes (adverse clinical events).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
-
C07AA · Product
- Pharmaceutical form
- PHF00082MIG
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AA — BETA BLOCKING AGENTS, NON-SELECTIVE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
C07AG · Product
- Pharmaceutical form
- PHF00009MIG
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AG — ALPHA AND BETA BLOCKING AGENTS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
C07AB · Product
- Pharmaceutical form
- PHF00082MIG
- Route of administration
- ORAL
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- C07AB — BETA BLOCKING AGENTS, SELECTIVE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Casa Del Corazon
- Sponsor organisation
- Fundacion Casa Del Corazon
- Address
- Calle Nuestra Senora De Guadalupe 5
- City
- Madrid
- Postcode
- 28028
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Casa Del Corazon
- Contact name
- Dr Fernando Alfonso Manterola
Public contact point
- Organisation
- Fundacion Casa Del Corazon
- Contact name
- Dr Fernando Alfonso Manterola
Locations
1 EU/EEA country · 27 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 200 | 27 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario De La Princesa
Cardiología, Calle De Diego De Leon 62, 28006, Madrid
University Clinical Hospital Virgen De La Arrixaca
Cardiología, Carretera De Cartagena Sn, El Palmar, Murcia
Hospital Universitario La Paz
Cardiología, Paseo Castellana 261, 28046, Madrid
Complexo Hospitalario Universitario De Santiago
Cardiología, Calle Choupana Da S/n, 15706, Santiago De Compostela
Hospital Universitario De La Princesa
Cardiología, Calle De Diego De Leon 62, 28006, Madrid
Hospital Clinico San Carlos
Cardiología, Calle Del Profesor Martin Lagos Sn, 28040, Madrid
Hospital Universitario Marques De Valdecilla
Cardiología, Avenida Valdecilla Sn, 39008, Santander
Hospital Clinico Universitario De Valencia
Cardiología, Avenida Blasco Ibanez 17, 46010, Valencia
Hospital Universitario Central De Asturias
Cardiología, Avenida De Roma S/n, 33011, Oviedo
Hospital Germans Trias I Pujol
Cardiología, Carretera Canyet 1a Planta, 08916, Badalona
Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida
Cardiología, Avinguda De L'alcalde Rovira Roure 80, 25196, Lleida
Hospital Clinic De Barcelona
Cardiología, Calle Villarroel 170, 08036, Barcelona
Complexo Hospitalario Universitario De Vigo
Cardiología, Estrada Clara Campoamor N 341, 36312, Vigo
Hospital Universitario 12 De Octubre
Cardiología, Bloque D, Avenida De Cordoba Sn, Madrid
Hospital General Universitario Gregorio Maranon
Cardiología, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Fundacion Jimenez Diaz
Cardiología, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Hospital Clinico Universitario De Valladolid
Cardiología, Avenida Ramon Y Cajal 3, 47003, Valladolid
Hospital Universitario Ramon Y Cajal
Cardiología, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
Hospital Universitario Puerta De Hierro De Majadahonda
Cardiología, Calle De Manuel De Falla 1, 28222, Majadahonda
Hospital Universitario De Toledo
Cardiología, Avenue Del Rio Guadiana Sn, 45007, Toledo
Bellvitge University Hospital
Cardiología, Carrer De La Feixa Llarga S/n, 08907, L'hospitalet De Llobregat
Complexo Hospitalario Universitario A Coruna
Cardiología, Lugar Jubias De Arriba 84, 15006, A Coruna
Hospital Universitari Vall D Hebron
Cardiología, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital Universitario Y Politecnico La Fe
Cardiología, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital General Universitario Reina Sofia
Cardiología, Avenida Menendez Pidal S/n, 14004, Cordoba
Hospital De La Santa Creu I Sant Pau
Cardiología, Calle De San Antonio Maria Claret 167, 08025, Barcelona
Hospital Universitario De Torrejon
Cardiología, Calle De Mateo Inurria 1, 28850, Torrejon De Ardoz
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2024-07-08 | 2024-10-22 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 20 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-510213-25-00_Public | 1 |
| Protocol (for publication) | D1_Protocol_V2_ 2023-510213-25-01_Public | 2 |
| Protocol (for publication) | D2_Protocol modification 1_2023-510213-25-01_clean version | 3 |
| Protocol (for publication) | D2_Protocol modification 1_2023-510213-25-01_TC | 3 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements 2023-510213-25-00_Public | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult _V2_050224_Censured | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult_V3_20250128_Clean version | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adult_V3_20250128_TC | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF description_2023-510213-25-00_Public | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Carvedilol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Carvedilol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Carvedilol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Nebivolol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Nebivolol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Nebivolol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Propanolol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Propanolol EFG 2023-510213-25-00 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Propranolol EFG 2023-510213-25-00 | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol BetaTAKO Synopsis_V2_070224_Public | 2 |
| Synopsis of the protocol (for publication) | D1_ ProtocolBetaTAKO Synopsis_V1_111223_Public | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-23 | Spain | Acceptable 2024-03-25
|
2024-03-25 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-01-28 | Spain | Acceptable 2025-03-27
|
2025-03-28 |