MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy

Not Applicable

Completed

Conditions: Congestive Heart Failure
Tachycardia

Interventions: Device: Cardiac resynchronization therapy with defibrillation
Device: Implantable Cardioverter Defibrillator (ICD)

Registration Number: NCT00180271

Lead Sponsor: Boston Scientific Corporation

Brief Summary: The MADIT-CRT trial is designed to determine if combined implantable cardiac defibrillator (ICD)-cardiac resynchronization therapy (CRT-D) will reduce the risk of mortality and heart failure (HF) events by approximately 25%, in subjects who are in New York Heart Association (NYHA) functional Class II with non-ischemic or ischemic cardiomyopathy and subjects who are in NYHA functional Class I with ischemic cardiomyopathy, left ventricular dysfunction (ejection fraction \[EF\] \< or = 0.30), and prolonged intraventricular conduction (QRS duration \> or = 130 ms).

Detailed Description: In this study, subjects will be randomized to CRT-D or ICD-only. Randomization will be stratified by clinical center and ischemic status. Approximately 60% of the subjects will be randomly assigned to receive a CRT-D with biventricular pacing, and 40% will receive an ICD only. Optimal pharmacological therapy for heart failure will be required in both treatment arms. Length of follow-up for each subject will depend on the date of entry into the study, since all subjects will be followed to a common study termination date.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1820

Inclusion Criteria

Ischemic heart disease defined as:
- NYHA Class I or II for the past 3 calendar months prior to, and at the time of, enrollment;
- one or more clinically documented (Q wave or enzyme positive) prior myocardial infarctions, but not within 3 calendar months of enrollment; and/or
- one or more prior coronary artery bypass graft surgeries or percutaneous coronary interventions (balloon and/or stent angioplasty) but not within 3 calendar months of enrollment.

Non-ischemic heart disease including dilated cardiomyopathy characterized by a low ejection fraction and increased ventricular volume, with ventricular compliance that is normal or increased
NYHA Class II for the past 3 calendar months prior to, and at the time of, enrollment

AND all of the following:

Stable optimal pharmacologic therapy.
An ejection fraction < or = 0.30 by angiographic, radionuclide, or echocardiographic methods within one year prior to enrollment and measured during the enrollment echocardiogram obtained within 14 days prior to randomization to confirm eligibility (recommended)
Resting QRS duration > or = 130 ms on print-out of a current electrocardiogram (ECG) obtained within 14 days prior to randomization.
Sinus rhythm by ECG (including right bundle branch block [RBBB] and first degree heart block with PR < 250 ms.)
Men and women 21 years of age or older (no upper-age cut off)

Exclusion Criteria

Existing indication for CRT
Subjects with an implanted pacemaker
Subjects with an existing ICD or CRT device
Subjects in NYHA Class I with non-ischemic cardiomyopathy
Subjects in NYHA Class III or IV in the past 3 calendar months prior to, or at the time of, enrollment
Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past 3 calendar months prior to enrollment
Enzyme-positive myocardial infarction within the past 3 calendar months prior to enrollment
Subjects with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the foreseeable future
Subjects with second or third degree heart block
Subjects with irreversible brain damage from preexisting cerebral disease
Women who are pregnant or plan to become pregnant during the course of the trial. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
Reversible non-ischemic cardiomyopathy such as acute viral myocarditis or discontinuation of alcohol in alcohol-induced heart disease
Subjects with chronic atrial fibrillation within one month prior to enrollment
Presence of any disease, other than the subject's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial, e.g., cancer, uremia (blood urea nitrogen [BUN] > 70 mg/dl or creatinine > 3.0 mg/dl), liver failure, etc.
Subjects participating in any other clinical trials
Subjects unwilling or unable to cooperate with the protocol
Subjects who live at such a distance from the clinic that travel for follow-up visits would be unusually difficult
Subjects who do not anticipate being residents of the area for the scheduled duration of the trial
Subjects unwilling to sign the consent for participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRT-D	Cardiac resynchronization therapy with defibrillation	CRT-D: Cardiac resynchronization therapy with defibrillation.
ICD	Implantable Cardioverter Defibrillator (ICD)	ICD: Implantable cardioverter defibrillator

Primary Outcome Measures

Name	Time	Method
Mortality From Any Cause or First Heart Failure (HF) Event	Outcome measured at average follow-up duration of 2.4 years.	MADIT-CRT was an event-driven trial in which patients were monitored for all-cause mortality and HF events. An HF event was defined as either hospitalization for symptoms and/or signs consistent with congestive HF and: 1. administration of intravenous decongestive therapy that does not involve formal in-patient hospital admission, regardless of the setting (i.e. in an emergency room setting, in the physician's office, etc.), or 2. administration of an augmented HF regimen with oral or intravenous medications during an in-hospital stay.

Secondary Outcome Measures

Name	Time	Method
Recurrent Heart Failure Events	Time of event, DSMB review	The MADIT-CRT secondary outcome evaluated the effects of CRT-D, relative to ICD, on the recurrence of heart failure events over the full study period An HF event was defined as either hospitalization for symptoms and/or signs consistent with congestive HF and: 1. administration of intravenous decongestive therapy that does not involve formal in-patient hospital admission, regardless of the setting (i.e. in an emergency room setting, in the physician's office, etc.), or 2. administration of an augmented HF regimen with oral or intravenous medications during an in-hospital stay.