Heart Failure, Primary Prevention of Sudden Cardiac Death, Implantable Cardioverter Defibrillator
Conditions
Keywords
Heart Failure, Prevention strategy of Sudden Cardiac Death, Implantable cardioverter defibrillator, Heart Failure Optimal Therapy, Mortality
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 ≥ 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
DEVICEICD 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.
DEVICENo 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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
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.
Intervention model description
This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Contacts
CONTACTAlexandra BRUNEAU, Mrs
CONTACTEloi MARIJON, MD, PhD
PRINCIPAL_INVESTIGATOREloi MARIJON, MD, PhD
AP-HP, Hôpital européen Georges Pompidou, Paris
STUDY_DIRECTORRodrigue GARCIA, MD, PhD
CHU Poitiers, France
Outcome results
None listed