Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 70 Years (DILEMMA)

Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 70 Years: A Randomized Controlled Trial

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 ≥ 70 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Implantable Cardioverter Defibrillator; Primary Prevention of Sudden Cardiac Death
• Intervention / Treatment: Device: No ICD implantation; Device: ICD implantation

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 ≥ 70 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.

• Study Type: Interventional
• Enrollment (Estimated): 730
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandra BRUNEAU, Mrs; Phone Number: +33144841712; Email: alexandra.bruneau@aphp.fr
• Study Contact Backup: Name: Eloi MARIJON, MD, PhD; Phone Number: +33156093692; Email: eloi.marijon@aphp.fr

Study Locations

• France
  • Aix-en-Provence, France, 13616
    • Recruiting
    • Centre Hospitalier d'Aix en Provence
    • Contact: Jérôme TAIEB, MD; Phone Number: 04 42 33 50 53; Email: jtaieb@ch-aix.fr
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens-Picardie-Site sud
    • Contact: Alexis HERMIDA-JARRY, MD; Email: hermida.alexis@chu-amiens.fr
  • Brest, France, 29200
    • Recruiting
    • CHU Brest - Hopital La Cavale Blanche
    • Contact: Jacques MANSOURATI, Pr; Phone Number: 02 98 34 73 73; Email: jacques.mansourati@chu-brest.fr
  • Créteil, France, 94000
    • Recruiting
    • HôpitalHenri Mondor
    • Contact: Nicolas LELLOUCHE, MD, PhD; Phone Number: 0149814350; Email: nicolas.lellouche@aphp.fr
  • La Tronche, France, 38700
    • Recruiting
    • Chu Grenoble Alpes
    • Contact: Pascal DEFAYE, MD, PhD; Phone Number: 04 76 76 75 75; Email: pdefaye@chu-grenoble.fr
  • Lomme, France, 59462
    • Recruiting
    • Groupement d'Hôpitaux de l'Institut Catholique de Lille
    • Contact: Aymeric MENET, MD; Phone Number: 03 20 22 50 57; Email: menet.aymeric@ghicl.net
  • Marseille, France, 13385
    • Recruiting
    • Hopital de la Timone
    • Contact: Jean Claude DEHARO, MD, PhD; Phone Number: 04 91 38 65 90; Email: jean-claude.deharo@ap-hm.fr
  • Nancy, France, 54710
    • Recruiting
    • Hôpital de Brabois
    • Contact: Mathieu ECHIVARD, MD; Email: m.echivard@chru-nancy.fr
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes
    • Contact: Vincent PROBST, MD, PhD; Phone Number: 02 40 16 50 08; Email: vincent.probst@chu-nantes.fr
  • Paris, France, 75013
    • Recruiting
    • Hopital Pitie-Salpetriere
    • Contact: Estelle GANDJBAKHCH, MD, PhD; Phone Number: 01 42 16 30 55; Email: estelle.gandjbakhch@aphp.fr
  • Paris, France, , 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Contact: Eloi MARIJON, MD, PhD; Phone Number: 01 56 09 36 92; Email: eloi.marijon@aphp.fr
  • Paris, France, 75014
    • Recruiting
    • Hôpital Bichat - Claude Bernard
    • Contact: Fabrice EXTRAMIANA, MD, PhD; Phone Number: 0140258236; Email: fabrice.extramiana@aphp.fr
  • Poitiers, France, 86021
    • Recruiting
    • CHU Poitiers
    • Contact: Rodrigue Garcia, MD, PhD; Email: rodrigue.garcia@chu-poitiers.fr
  • Rennes, France, 35033
    • Recruiting
    • Hôpital Pontchaillou
    • Contact: Christophe LECLERCQ, MD; Phone Number: 0299282525; Email: christophe.leclercq@chu-rennes.fr
  • Rouen, France, 76000
    • Recruiting
    • CHU de Rouen
    • Contact: Frédéric ANSELME, MD, PhD; Phone Number: 02 32 88 81 11; Email: frederic.anselme@chu-rouen.fr
  • Saint-Denis, France, 93207
    • Recruiting
    • Centre Cardiologique du Nord
    • Contact: Olivier PIOT, MD; Phone Number: 01 49 33 41 82; Email: o.piot@ccn.fr
  • Strasbourg, France, 67200
    • Recruiting
    • CHU Strasbourg
    • Contact: Laurence JESEL-MOREL, MD, PhD; Phone Number: 03 69 55 09 48; Email: laurence.jesel-morel@chru-strasbourg.fr
  • Toulouse, France, 31076
    • Recruiting
    • Clinique Pasteur
    • Contact: Serge BOVEDA, MD, PhD; Phone Number: 05 62 21 16 45; Email: sboveda@clinique-pasteur.com
  • Tours, France, 37170
    • Recruiting
    • Hôpital Trousseau
    • Contact: Laurent FAUCHIER, MD; Phone Number: 02 47 47 87 83; Email: laurent.fauchier@univ-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥70 years old,
• Left ventricular ejection fraction ≤ 35%, assessed by echocardiography, single-photon emission computed tomography and radionuclide ventriculography and/or cardiac magnetic resonance (CMR) (assessed at inclusion or within the 6 weeks prior to inclusion).
• NYHA class II or III
• Heart failure HFOT ≥ 3 months (Possible exceptions : possibility of including patients who do not tolerate the maximum dose or who do not tolerate all four therapeutic classes, as well as the possibility of not waiting for three months when one of the classes is discontinued or when dosage adjustments are made due to poor tolerance ...)
• Providing informed consent
• Affiliated to a French Health Insurance system.

Exclusion Criteria:

• Enrolled in or planning to enroll in a conflicting interventional trial (trial evaluating the interest of ICD or modifying HFOT outside the last ESC Guidelines)
• 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 (cerebrovascular disease with functional repercussions or effect on the patient's autonomy)
• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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.	48 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular mortality	Rate of cardiovascular mortality assessed by a blinded endpoint committee.	48 months after randomization
Sudden cardiac death and death from ventricular arrhythmias	Rate of sudden cardiac death and rate of death from ventricular arrhythmias assessed by a blinded endpoint committee.	48 months after randomization
Unplanned hospitalization due to cardiovascular causes	Number of unplanned hospitalization due to cardiovascular causes	48 months after randomization
ICD related complications including inappropriate therapies	Number of ICD related therapies (antitachycardia pacing and shocks), hematoma, infection related to the device, lead dislodgement requiring intervention, pneumothorax and tamponade.	48 months after randomization
Global quality of life score with 36-Item Short Form Survey (SF36)	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.	baseline, 6, 12, 24, 36 and 48 months
Health-related quality of life score Euroqol EQ-5D questionnaire	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)	baseline, 6, 12, 24, 36 and 48 months
Patient's global self-assessment of heart failure-related quality of life score	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.	baseline, 6, 12, 24, 36 and 48 months
The Incremental cost-utility ratio. (ICUR)	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.	48 months
The incremental cost-effectiveness ratio (ICER)	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.	48 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Eloi MARIJON, MD, PhD, AP-HP, Hôpital Européen Georges Pompidou, Paris; Study Director: Rodrigue GARCIA, MD, PhD, CHU Poitiers, France

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Mortality; Implantable cardioverter defibrillator; Prevention strategy of Sudden Cardiac Death; Heart Failure Optimal Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: APHP200035; 2021-A01959-32 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasability and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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