Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator

Study Overview
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Brief Summary
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The MADIT S-ICD trial is designed to evaluate if subjects with a prior myocardial infarction, diabetes mellitus and a relatively preserved ejection fraction of 36-50% will have a survival benefit from receiving a subcutaneous implantable cardioverter defibrillator (S-ICD) when compared to those receiving conventional medical therapy.

Detailed Description
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In this study, subjects will be randomized to receive a subcutaneous implantable cardioverter defibrillator or Conventional Medical Therapy (CMT). Randomization will be stratified by enrolling site, in a 2:1 (S-ICD:CMT) scheme. Length of follow-up for each subject will be dependent on the date of entry into the study, since all subjects will be followed to a common study termination date.

Official Title
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Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD)

Conditions
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Tachycardia, Diabetes Mellitus, Cardiovascular Disease

Intervention / Treatment
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* Device: Subcutaneous Implantable Cardioverter Defibrillator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years on date of consent Diabetes mellitus treated with oral hypoglycemic agents, non-insulin injectable and/or insulin for the past 3 calendar months or longer prior to consent date LV ejection fraction (LVEF) of 36-50% documented by imaging (preferably by MRI or echocardiographic methods), within 12 calendar months before consent date and at least 3 calendar months after most recent Myocardial Infarction (MI), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). One or more clinically documented, enzyme-positive myocardial infarctions, more than 3 calendar months prior to consent date*. (If enzyme information and clinical documentation is not available, there must be a clear evidence of prior silent myocardial infarction identified as either new pathologic Q waves on ECG or imaging documentation of an infarcted area (left ventricular angiography/ nuclear scan/ MRI) Note: MI qualification based on the Universal Definition of MI) Qualifying 12-lead ECG within 6 calendar months before consent date and at least 3 calendar months after most recent MI, PCI or CABG. (The qualifying ECG* can be sinus rhythm or atrial fibrillation (patients with persistent or permanent atrial fibrillation should have a controlled ventricular response <100 bpm on consent date) *QRS duration on the qualifying ECG >90 msec) Passing S-ICD Screening ECG performed per applicable user's manual on or after the consent date that identifies one or more qualifying S-ICD sensing vectors Exclusion Criteria: Ejection fraction >50% or <36% within 12 calendar months prior to consent date and at least 3 calendar months after the most recent MI, PCI or CABG Existing guideline based indication for an implantable cardioverter defibrillator (ICD), pacemaker, cardiac resynchronization therapy device (CRT), or cardiac resynchronization therapy device with defibrillator (CRT-D) therapy Existing or previously implanted ICD, CRT, CRT-D, or pacemaker device system Active infection at the time of consent Contraindication for S-ICD implantation according to the S-ICD pulse generator (PG) User's Manual Hemodialysis and/or peritoneal dialysis at the time of enrollment New York Heart Association Class IV in the past 3 calendar months prior to or at the time of consent date Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within 3 calendar months prior to the consent date Enzyme-positive myocardial infarction or silent myocardial infarction diagnosed within 3 calendar months prior to the consent date Unstable angina with need for outpatient treatment or hospitalization (change/addition of anti-anginal medication and/or coronary revascularization), within 3 calendar months prior to the consent date Angiographic evidence of coronary disease in a patient that is a candidate for coronary revascularization and is likely to undergo CABG or PCI in the next 3 calendar months High risk for arterial embolism (e.g. presence of mobile left ventricular thrombus) Hemodynamically significant congenital heart disease, aortic valvular heart disease, or amyloid heart disease Baseline body mass index > 45 kg/m2 On a heart transplant list or likely to undergo heart transplant within one calendar year Presence of any other disease, other than the subject's cardiac disease, that in the opinion of the investigator is likely to significantly reduce the patient's likelihood of survival for the duration of the trial (e.g. cancer, liver failure). Unwillingness or inability to cooperate with the protocol Resides at such a distance from the enrolling site so travel to follow-up visits would be unusually difficult Reversible causes of heart disease (e.g. viral myocarditis or tachycardia induced cardiomyopathy) Participation in other clinical trials (observational registries are allowed with approval from the CDC) Does not anticipate residing in the vicinity of the enrolling site for the duration of the trial Unwillingness to sign the consent for participation

Ages Eligible for Study
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Minimum Age: 65 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 |
| --- | --- |
| No Intervention: Conventional Medical Therapy<br>This arm of the trial continues with their current conventional medical therapy. | |
| Active Comparator: Subcutaneous Implantable Cardioverter Defibrillator<br>This arm of the trial receives a subcutaneous implantable defibrillator. | Device: Subcutaneous Implantable Cardioverter Defibrillator<br>* The S-ICD is an entirely subcutaneous implantable cardioverter defibrillator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality | This study is event driven so there is no set end date for follow-up or analysis. Subjects will be followed until the statistical boundary is crossed. | Through study completion,estimated average of 2.6 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-Cause Mortality in various subgroups | This study is event driven so there is no set end date for follow-up or analysis. Subjects will be followed until the statistical boundary is crossed. | Through study completion,estimated average of 2.6 years follow-up | 
| Sudden Death in various subgroups | This study is event driven so there is no set end date for follow-up or analysis. Subjects will be followed until the statistical boundary is crossed. | Through study completion,estimated average of 2.6 years follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous, Implantable Cardioverter Defibrillator, MADIT, Diabetes, Myocardial Infarction