Study of Personalized Allocation of Defibrillators in Non-ischemic Heart Failure (SPANISH-1)

Prospective, randomised, multicentre, open-label study to assess the non-inferiority of a personalised precision strategy for Sudden Cardiac Death (SCD) prevention in patients with non-ischemic dilated cardiomyopathy with Left Ventricular Ejection Fraction (LVEF) ≤35%

Study Overview

• Status: Recruiting
• Conditions: Non-ischemic Dilated Cardiomyopathy
• Intervention / Treatment: Other: Control Strategy; Other: Personalized precision ICD implantation Strategy based in genetic findings and CMR results

Detailed Description

Prospective, randomised, multicentre, open-label study to assess the non-inferiority of a personalised precision strategy for SCD prevention in patients with non-ischemic dilated cardiomyopathy with LVEF≤35%

Randomization will be 1:1 and patients are allocated to either control strategy or intervention strategy.

In the control strategy group, patients will get an Implantable Cardioverter Defibrillator (ICD) implanted. Patients allocated to the intervention strategy will receive an ICD according to genetic and CMR results. ICD implantation criteria in patients allocated to the personalised strategy group will be the presence of either a Dilated Cardiomyopathy DCM-causing pathogenic or likely pathogenic genetic variants or Late Gadolinium Enhancement (LGE) in Cardiac Magnetic Resonance (CMR). Patients without DCM-associated genetic variants and without LGE on CMR will not receive standard treatment but an ICD will not be implanted on them.

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Projects Department (CIBER); Phone Number: +34 91 822 28 74; Email: proyectos@ciberisciii.es
• Study Contact Backup: Name: Maria de la Iglesia; Phone Number: +34911916749; Email: spanish-i@cibercv.es

Study Locations

• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General Universitario Dr Balmis
    • Principal Investigator: Juan Gabriel Martínez
  • Barcelona, Spain
    • Recruiting
    • H.U. Vall d'Hebron
    • Principal Investigator: Nuria Rivas Gándara
  • Barcelona, Spain, 08025
    • Recruiting
    • H.U. de la Santa Creu i Sant Pau
    • Principal Investigator: José M Guerra Ramos
  • Barcelona, Spain, 08036
    • Not yet recruiting
    • H. Clinic de Barcelona
    • Principal Investigator: Josep Lluis Mont Girbau
  • Barcelona, Spain, 08916
    • Recruiting
    • H.U. Germans Trias i Pujol
    • Principal Investigator: Antoni Bayes Genis
  • Gerona, Spain, 17007
    • Recruiting
    • H.U. Josep Trueta
    • Principal Investigator: Ramón Brugada Terradellas
  • Granada, Spain, 18014
    • Not yet recruiting
    • H.U. Virgen de las Nieves
    • Principal Investigator: Juan Jiménez Jáimez
  • Lérida, Spain, 25198
    • Recruiting
    • Hospital Arnau de Vilanova
    • Principal Investigator: Jara Gayán Ordás
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
    • Principal Investigator: Borja Ibáñez Cabeza
  • Madrid, Spain, 28007
    • Recruiting
    • H.G.U. Gregorio Marañón
    • Principal Investigator: Javier Bermejo Thomas
  • Madrid, Spain, 28034
    • Not yet recruiting
    • H.U. Ramón y Cajal
    • Principal Investigator: Marta Jiménez-Blanco Bravo
  • Madrid, Spain, 28040
    • Recruiting
    • H. Clínico San Carlos
    • Principal Investigator: Victoria Cañadas Godoy
  • Madrid, Spain, 28041
    • Recruiting
    • H.U. 12 de Octubre
    • Principal Investigator: Fernando Arribas Ynsaurriaga
  • Murcia, Spain, 30120
    • Recruiting
    • H.C.U. Virgen de la Arrixaca
    • Principal Investigator: Domingo Pascual Figal
  • Málaga, Spain, 29010
    • Recruiting
    • H.U. Virgen de la Victoria
    • Principal Investigator: José Manuel García-Pinilla
  • Palma De Mallorca, Spain, 07198
    • Recruiting
    • H.U. Son Llátzer
    • Principal Investigator: Tomás Ripoll Vera
  • Pamplona, Spain, 31008
    • Recruiting
    • Complejo Hospitalario de Navarra
    • Principal Investigator: Maria Teresa Basurte Elorz
  • Salamanca, Spain, 37007
    • Recruiting
    • H.U de Salamanca
    • Principal Investigator: Pedro Luis Sánchez Fernández
  • Sevilla, Spain, 41013
    • Recruiting
    • H.U. Virgen del Rocio
    • Principal Investigator: Eduardo Arana Rueda
  • Toledo, Spain, 45007
    • Not yet recruiting
    • Complejo Hospitalario Universitario de Toledo
    • Principal Investigator: Miguel Ángel Arias Palomares
  • Valencia, Spain, 46014
    • Not yet recruiting
    • Hospital General Universitario de Valencia
    • Principal Investigator: Aurelio Quesada Dorador
  • Valencia, Spain, 46010
    • Not yet recruiting
    • H.C.U de Valencia
    • Principal Investigator: Julio Nunez Villota
  • Valencia, Spain, 46010
    • Recruiting
    • H.U. Politécnico de la Fe
    • Principal Investigator: Luis Martínez Dolz
  • Valladolid, Spain, 47003
    • Recruiting
    • H.C.U de Valladolid
    • Principal Investigator: José Alberto San Román Calvar
  • Zaragoza, Spain, 50009
    • Not yet recruiting
    • H.U. Miguel Servet
    • Principal Investigator: Maria del Rosario Ortas Nadal
  • A Coruña
    • Santiago De Compostela, A Coruña, Spain, 15706
      • Recruiting
      • H.C.U de Santiago de Compostela
      • Principal Investigator: J. Ramón González-Juanatey
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Recruiting
      • H.U. Central de Asturias
      • Principal Investigator: Rebeca Lorca Gutiérrez
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • H.U. de Bellvitge
      • Principal Investigator: José González Costello
    • Sabadell, Barcelona, Spain, 08208
      • Not yet recruiting
      • Hospital Parc Tauli
      • Principal Investigator: Amadeo Marcelo Rizzo
  • La Coruña
    • A Coruña, La Coruña, Spain, 15006
      • Not yet recruiting
      • H.U. A Coruña
      • Principal Investigator: Maria Generosa Crespo Leiro
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Recruiting
      • H.U. Puerta de Hierro
      • Principal Investigator: Pablo García Pavía

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years at the time of screening.
• Previously established diagnosis of Non-ischemic DCM
• Optimised medical treatment at maximum tolerated doses for at least 3 months prior to the screening date.
• NYHA functional class II-III.
• LVEF ≤ 35% documented by CMR as study procedure.
• Life expectancy greater than 12 months.

Exclusion Criteria:

• History of coronary artery disease justifying the presence of ventricular dysfunction, defined as: history of coronary revascularisation or presence of significant coronary stenosis (≥50% in left main or ≥70% in a major epicardial artery) on invasive or non-invasive coronary angiography (coronary CT)
• Left ventricular dysfunction attributed to congenital heart disease, valvular disease, alcohol abuse or chemotherapy.
• Hypertrophic or infiltrative cardiomyopathy, active myocarditis or constrictive pericarditis.
• History of recovered sudden death or sustained ventricular tachycardia.
• NYHA functional class IV.
• Waiting list for cardiac transplantation in emergency 0.
• Receiver of a solid organ transplant (lung, liver, heart or kidney).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control Strategy	Other: Control Strategy; ICDs will be implanted in all patients according to current recommendations
Experimental: Personalized precision ICD implantation Strategy based in genetic findings and CMR results	Other: Personalized precision ICD implantation Strategy based in genetic findings and CMR results; Patients allocated to the intervention strategy will receive an ICD according to genetic and CMR results. ICD implantation criteria in patients allocated to the personalised strategy group will be the presence of either a DCM-causing pathogenic or likely pathogenic genetic variants or LGE in CMR. Patients without DCM-associated genetic variants and without LGE on CMR will not receive standard treatment but an ICD will not be implanted on them.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite end-point of all cause death, hospitalization due to device-related complications, and non-fatal major arrhythmic events.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death		4 years
SCD		4 years
Hospitalisation for device-related complications		4 years
Non-fatal major arrhythmic events		4 years
cost-effectiveness	Incremental Cost-effectiveness ratio (ICER) of personalized ICD allocation strategy in non-ischemic DCM [ Time Frame: The time horizon of the evaluation will be limited to 4 years ] The ICER of the personalized ICD allocation strategy compared with standard strategy is defined as the ratio between the variation in costs and the variation in effectiveness between both strategy groups. In the personalized strategy group, costs will include those related to personalization tests (CMR and genetic analysis) plus costs related to implanting and carrying an ICD (in the number of patients who eventually receive a device). In the control group, costs will include only the latter concept. Costs will be measured in Euros. The variation in effectiveness will be measured both in terms of life years gained, measured in years, and in terms of quality of life gained, measured in QALY. In the first case, ICER will be measured as Euros/year; in the second, it will be measured as Euros/QALY.	4 years
Quality of life assessed by KCCQ, EQ-5D and HADS		4 years

Collaborators and Investigators

• Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Pablo García Pavía, H.U. Puerta de Hierro, Majadahonda; Principal Investigator: Antoni Bayés Genís, H.U. Germans Trias i Pujol; Principal Investigator: Javier Bermejo Thomas, H.G.U. Gregorio Marañón; Principal Investigator: Javier Díez Martínez, University of Navarra

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: SPANISH-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No