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

Heart Failure Clinical Trial

— DILEMMA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05373940
• Other study ID #: APHP200035
• Secondary ID: 2021-A01959-32
• Status: Recruiting
• Phase: N/A
• Start date: June 29, 2022
• Est. completion date: May 31, 2030

Study information

• Verified date: November 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Alexandra BRUNEAU, Mrs
• Phone: +33144841712
• Email: alexandra.bruneau[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 730
• Est. completion date: May 31, 2030
• Est. primary completion date: May 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Death
• Death, Sudden, Cardiac
• Heart Failure
• Implantable Cardioverter Defibrillator
• Primary Prevention of Sudden Cardiac Death

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Centre Hospitalier d'Aix en provence	Aix-en-Provence
France	CHU Amiens-Picardie-Site sud	Amiens
France	HôpitalHenri Mondor	Créteil
France	CHU Grenoble Alpes	La Tronche
France	Groupement d'Hôpitaux de l'Institut Catholique de Lille	Lomme
France	Hôpital de La Timone	Marseille
France	Hôpital de Brabois	Nancy
France	CHU de Nantes	Nantes
France	Hôpital Privé du Confluent	Nantes
France	Hôpital Bichat - Claude Bernard	Paris
France	Hôpital européen Georges Pompidou	Paris
France	Hôpital Pitié-Salpétrière	Paris
France	CHU Poitiers	Poitiers
France	Hôpital Pontchaillou	Rennes
France	CHU de Rouen	Rouen
France	Centre Cardiologique du Nord	Saint Denis
France	CHU Strasbourg	Strasbourg
France	Clinique Pasteur	Toulouse
France	Hôpital Trousseau	Tours

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cardiovascular mortality	Rate of cardiovascular mortality assessed by a blinded endpoint committee.	48 months after randomization
Secondary	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
Secondary	Unplanned hospitalization due to cardiovascular causes	Number of unplanned hospitalization due to cardiovascular causes	48 months after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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