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

Official title

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

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

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.

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.

Primary outcome measures

• Overall survival [Time frame: 48 months after randomization]

Secondary outcome measures (9)

• Cardiovascular mortality [Time frame: 48 months after randomization]
• Sudden cardiac death and death from ventricular arrhythmias [Time frame: 48 months after randomization]
• Unplanned hospitalization due to cardiovascular causes [Time frame: 48 months after randomization]
• ICD related complications including inappropriate therapies [Time frame: 48 months after randomization]
• Global quality of life score with 36-Item Short Form Survey (SF36) [Time frame: baseline, 6, 12, 24, 36 and 48 months]
• Health-related quality of life score Euroqol EQ-5D questionnaire [Time frame: baseline, 6, 12, 24, 36 and 48 months]
• Patient's global self-assessment of heart failure-related quality of life score [Time frame: baseline, 6, 12, 24, 36 and 48 months]
• The Incremental cost-utility ratio. (ICUR) [Time frame: 48 months]
• The incremental cost-effectiveness ratio (ICER) [Time frame: 48 months]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

France · 19 centers

• Centre Hospitalier d'Aix en provence — Aix-en-Provence
• CHU Amiens-Picardie-Site sud — Amiens
• CHU Brest - Hôpital La Cavale Blanche — Brest
• HôpitalHenri Mondor — Créteil
• CHU Grenoble Alpes — La Tronche
• Groupement d'Hôpitaux de l'Institut Catholique de Lille — Lomme
• Hôpital de La Timone — Marseille
• Hôpital de Brabois — Nancy
• … and 11 more centers

Identifiers

NCT: NCT05373940 · APHP200035 · 2021-A01959-32

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗