Efficacy and Safety of Implantable Cardioverter-Defibrillator (ICD) Implantation in the Elderly

Study Overview
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Brief Summary
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The overall aim of this trial is to study the safety and efficacy of ICD implantation as a primary prevention strategy of sudden cardiac death in patients 70 years and older. This study will assess the many competing factors involved with ICD implantation including 1) the impact on mortality, especially in the context of a declining rate of sudden death with advanced age, 2) the tolerability of the powerful therapeutic action of the device, and 3) the impact on quality of life.

Detailed Description
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The overall aim of this trial is to study the safety and efficacy of ICD implantation as a primary prevention strategy of sudden cardiac death (SCD) in patients 70 years and older. In particular, this study is designed to determine the comparative effectiveness of ICD, in addition to optimal medical therapy (OMT), in reducing all-cause mortality, versus OMT alone; OMT includes standard intervention for chronic heart failure patients, i.e. lifestyle modification, disease management, adoption of healthy diet and exercise practices, etcetera. One particularly important secondary objective is to assess treatment efficacy under the conditions of high versus low co-morbidity burden. Participants will be randomized (1:1 ratio) to ICD + OMT or OMT alone, and stratified by participating site and co-morbidity level (Charlson score <3 versus 3+). Acute treatment visits will occur as clinically indicated and per local convention; follow-up will occur 1-4 months post-randomization (all participants), and not sooner than 30 days - and not later than 120 days post-implantation (ICD arm); regular follow-up will occur at 6 month intervals post-randomization until study close (all participants). All follow-up will be conducted centrally. Neither the participant nor treating clinician will be masked to treatment. Primary Objective: The primary objective of this study is to determine if a primary prevention strategy with ICD implantation in addition to optimal medical therapy (OMT) is effective in reducing all-cause mortality compared to OMT alone in patients 70 years of age and older who are eligible for ICD therapy according to current Centers for Medicare & Medicaid Services (CMS) criteria. Primary Hypothesis: The primary hypothesis of this study is that implantation of an ICD plus optimal medical therapy will reduce all-cause mortality in patients 70 years of age and older versus optimal medical therapy alone. Secondary Objectives: One secondary objective of this study is to ascertain whether age, co-morbidity burden, or age and burden together, are determinants in mortality outcomes in the OMT versus ICD + OMT group. An additional secondary objective of the study is to determine the effect of ICD implantation plus optimal medical therapy on quality of life among elderly patients compared with optimal medical therapy alone.

Official Title
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CSP #592 - Efficacy and Safety of ICD Implantation in the Elderly

Conditions
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Cardiomyopathy, Coronary Artery Disease, Congestive Heart Failure, Myocardial Infarction

Intervention / Treatment
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* Device: Implantable Cardioverter Defibrillator
* Other: Optimal Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 70 years of age or older Eligible for ICD implementation according to the CMS criteria for primary prevention by one of the following conditions: Documented prior MI and a measured left ventricular ejection fraction (LVEF) <=30% (includes New York Heart Association [NYHA] class I, II, or III) Coronary artery disease with a documented prior MI, a measured left ventricular ejection fraction <=35%, and inducible, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) at electrophysiology (EP) study Ischemic dilated cardiomyopathy (IDCM), documented prior MI, NYHA class II and III heart failure, and measured LVEF <=35% Non-ischemic dilated cardiomyopathy (NIDCM) > 3 months, NYHA Class II and III heart failure, and measured LVEF <=35% Stable condition on Optimal Medical Therapy Able and willing to provide informed consent to participate in this study Exclusion Criteria: Enrolled in or planning to enroll in a conflicting trial Receiving a bi-ventricular ICD device New York Heart Association class IV heart failure Cardiogenic shock or symptomatic hypotension while in stable baseline rhythm, Coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) within the past 3 months An MI within the past 40 days Clinical symptoms or findings that would make them a candidate for coronary revascularization Irreversible brain damage from pre-existing cerebral disease Any disease other than cardiac disease (e.g. cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year Circumstance that would prevent completion of the trial and follow-up activities, including medical condition

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>ICD implantation in addition to Optimal Medical Therapy | Device: Implantable Cardioverter Defibrillator<br>* The ICD and lead(s) will be FDA-approved.<br>|
| Active Comparator: 2<br>Optimal Medical Therapy | Other: Optimal Medical Therapy<br>* Guidance on lifestyle modification, exercise training, and disease management including review of American Heart Association (AHA) Guidelines for Primary Prevention of Cardiovascular Disease and Stroke.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality | Through study completion, starting from consent/baseline: average of 31 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life - Minnesota Living With Heart Failure Questionnaire | Minnesota Living with Heart Failure questionnaire. MLHF scoring: 0 points = Best QOL, 105 points = Worst QOL. | Measured at 12-months post-randomization | 
| Sudden Cardiac Death | Sudden Cardiac Death | Through study completion, starting from consent/baseline: average of 31 months. | 
| All-cause Hospitalization | Number of participants hospitalized during study follow-up | Through study completion, starting from consent/baseline: average of 31 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSP 592, ICD, cardiovascular, heart, aging, chronic diseases, multi-site trial, investigational device, cardiomyopathy, coronary artery disease, congestive heart failure, myocardial infarction, I-70, I70, elderly, defibrillator