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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Recruiting

CT.gov ID

NCT05373940

Collaborator

Ministry of Health, France (Other)

730

Enrollment

Locations

Arms

Anticipated Duration (Months)

38.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Primary Prevention of Sudden Cardiac Death Implantable Cardioverter Defibrillator	Device: ICD implantation Device: No ICD implantation	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

730 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial.This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial.

Masking:

Single (Outcomes Assessor)

Masking Description:

Three experts in cardiac electrophysiology and ICD will be in charge of uniformly approving, while blinded to the study group, ICD tracings, cardiovascular events, including specific causes of death, in order to validate the primary and secondary endpoints.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

May 31, 2030

Anticipated Study Completion Date :

May 31, 2030

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Overall survival [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 Outcome Measures

Cardiovascular mortality [48 months after randomization]
Rate of cardiovascular mortality assessed by a blinded endpoint committee.
Sudden cardiac death and death from ventricular arrhythmias [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 [48 months after randomization]
Number of unplanned hospitalization due to cardiovascular causes
ICD related complications including inappropriate therapies [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) [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 [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 [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) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Hospitalier d'Aix en provence	Aix-en-Provence	France	13616
2	CHU Amiens-Picardie-Site sud	Amiens	France	80054
3	HôpitalHenri Mondor	Créteil	France	94000
4	CHU Grenoble Alpes	La Tronche	France	38700
5	Groupement d'Hôpitaux de l'Institut Catholique de Lille	Lomme	France	59462
6	Hôpital de La Timone	Marseille	France	13385
7	Hôpital de Brabois	Nancy	France	54710
8	CHU de Nantes	Nantes	France	44093
9	Hôpital Privé du Confluent	Nantes	France	44277
10	Hôpital européen Georges Pompidou	Paris	France	, 75015
11	Hôpital Pitié-Salpétrière	Paris	France	75013
12	Hôpital Bichat - Claude Bernard	Paris	France	75014
13	CHU Poitiers	Poitiers	France	86021
14	Hôpital Pontchaillou	Rennes	France	35033
15	CHU de Rouen	Rouen	France	76000
16	Centre Cardiologique du Nord	Saint Denis	France	93207
17	CHU Strasbourg	Strasbourg	France	67200
18	Clinique Pasteur	Toulouse	France	31076
19	Hôpital Trousseau	Tours	France	37170

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris
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