Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 75 Years

Overview

The primary objective of DILEMMA study is to assess whether the "heart failure optimal therapy alone (HFOT)" strategy is non inferior to the "HFOT+ICD" strategy in terms of overall survival 48 months after randomization, in patients ≥ 75 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not.

Full Title of Study: “Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 75 Years: A Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: May 31, 2030

Detailed Description

Rationale Although not recognized by guidelines, there is no available data demonstrating the benefit of Implantable Cardioverter Defibrillator (ICD) for primary prevention strategy of Sudden Cardiac Death (SCD) in elderly. Nevertheless, ICD are currently implanted in this population by extending the results obtained in randomized trials involving younger subjects to the elderly. Finally, if the absence of implantation in the elderly was not inferior to the implantation of such a device, the non-implantation would avoid the device-related complications and decrease the health costs. Main objective The primary objective of DILEMMA study is to assess whether the "heart failure optimal therapy alone (HFOT)" strategy is non inferior to the "HFOT+ICD" strategy in terms of overall survival 48 months after randomization, in patients ≥ 75 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not. Design This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial. 730 patients will be included over 4 years. Follow up will last 4 years.

Interventions

  • Device: ICD implantation
    • This group will undergo an ICD implantation (type and manufacturer at the discretion of the local investigator) in addition to heart failure medical therapy optimization. Patients of the “HFOT+ICD” group will be scheduled for ICD implantation.
  • Device: No ICD implantation
    • Patients of the “HFOT alone” group will not undergo ICD implantation (except if they develop sustained ventricular arrhythmias and fulfil for secondary prevention ICD implantation), and continue with medical therapy optimization only.

Arms, Groups and Cohorts

  • Experimental: Heart failure optimal therapy alone (HFOT)
    • Heart failure Optimal therapy without implantable cardioverter defibrillator. This group will not undergo an ICD implantation. They will be treated according to the HFOT recommended in the latest guidelines.
  • Active Comparator: Heart failure optimal therapy (HFOT) + Implantable cardioverter defibrillator (ICD)
    • Optimal medical therapy + implantable cardioverter defibrillator (HFOT+ICD). This group will undergo an ICD implantation (standard of care), any brand, CE marked, implantable (lifelong), available and reimbursed in the French market (the type and manufacturer at the discretion of the local investigator) in addition to heart failure medical therapy optimization.

Clinical Trial Outcome Measures

Primary Measures

  • Overall survival
    • Time Frame: 48 months after randomization
    • The primary endpoint will be the overall survival at 48 months after randomization to “HFOT alone” group or “HFOT+ICD” group. There is an annual follow-up with precise date of the fatal event and specific cause of death adjudicated by the blinded event committee.

Secondary Measures

  • Cardiovascular mortality
    • Time Frame: 48 months after randomization
    • Rate of cardiovascular mortality assessed by a blinded endpoint committee.
  • Sudden cardiac death and death from ventricular arrhythmias
    • Time Frame: 48 months after randomization
    • Rate of sudden cardiac death and rate of death from ventricular arrhythmias assessed by a blinded endpoint committee.
  • Unplanned hospitalization due to cardiovascular causes
    • Time Frame: 48 months after randomization
    • Number of unplanned hospitalization due to cardiovascular causes
  • ICD related complications including inappropriate therapies
    • Time Frame: 48 months after randomization
    • Number of ICD related therapies (antitachycardia pacing and shocks), hematoma, infection related to the device, lead dislodgement requiring intervention, pneumothorax and tamponade.
  • Global quality of life score with 36-Item Short Form Survey (SF36)
    • Time Frame: baseline, 6, 12, 24, 36 and 48 months
    • Global quality of life score with SF36 (Short form 36 health survey) : the norm data is 0-100, the health related quality of life is increased as the scores are increased.
  • Health-related quality of life score Euroqol EQ-5D questionnaire
    • Time Frame: baseline, 6, 12, 24, 36 and 48 months
    • Health-related quality of life measured by using the European Quality Of Life (EQ-5D) auto-questionnaire. The digits for the five dimensions are combined into a 5-digit number that describes the patient’s health state. The visual analogue scale (VAS) records the patient’s self-rated health on a vertical axis from 0 (worst health) to 100 (best health)
  • Patient’s global self-assessment of heart failure-related quality of life score
    • Time Frame: baseline, 6, 12, 24, 36 and 48 months
    • The Minnesota Living with Heart Failure will be used to measure the subjects perception of how their heart failure affect their life. Norm data is 0-105 (21 items ; score 0-5), quality of life increases as scores decrease.
  • The Incremental cost-utility ratio. (ICUR)
    • Time Frame: 48 months
    • The ICUR is calculated by dividing the difference between the average costs of both groups by the difference in mean QALYs gained in both groups. The QALYs will be constructed with the EuroQoL-5D (EQ-5D) questionnaire and value sets.
  • The incremental cost-effectiveness ratio (ICER)
    • Time Frame: 48 months
    • The ICER will estimate the cost per additional survivor and is calculated by dividing the difference between the average costs of both groups by the difference in effectiveness (survival) between both groups.

Participating in This Clinical Trial

Inclusion Criteria

  • ≥75 years old, – Left ventricular ejection fraction ≤ 35% – NYHA class II or III – Heart failure HFOT ≥ 3 months – Providing informed consent – Affiliated to a French Health Insurance system. Exclusion Criteria:

  • Enrolled in or planning to enroll in a conflicting interventional trial – Prior unstable sustained ventricular arrhythmia requiring external cardioversion – Myocardial infarction within the 40 days – Coronary artery intervention (catheter or surgical) within 90 days – History of syncope in the previous 6 months – Advanced cerebrovascular disease – Cognitive impairment leading to the incapacity of consent – Any disease other than cardiac disease (e.g. cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year. – Patient under tutorship, curatorship, or legal safeguard – Persons deprived of their liberty by judicial or administrative decision (prisoner)

Gender Eligibility: All

Minimum Age: 75 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Collaborator
    • Ministry of Health, France
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Eloi MARIJON, MD, PhD, Principal Investigator, AP-HP, Hôpital européen Georges Pompidou, Paris
    • Rodrigue GARCIA, MD, PhD, Study Director, CHU Poitiers, France
  • Overall Contact(s)
    • Alexandra BRUNEAU, Mrs, +33144841712, alexandra.bruneau@aphp.fr

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