MIRACLE EF Clinical Study

MIRACLE EF Clinical Study

This study is looking at whether the electrical treatment provided by a special type of pacemaker called a Cardiac Resynchronization Therapy (CRT) pacemaker may keep a patient's heart failure from getting worse. When the lower heart chambers (i.e. ventricles) are electrically paced to beat together by the CRT pacemaker, blood may be pumped to the body more efficiently.

The CRT pacemaker being studied in this clinical trial is approved by the US Food and Drug Administration (FDA) for patients with moderate to severe heart failure, whose hearts pump blood inefficiently. In the MIRACLE EF study, patients who have heart failure with slightly less inefficient hearts will be observed to see if the electrical pacing treatment is better than not getting the treatment. This study is being conducted to support FDA approval of this type of pacemaker for people whose heart failure is less inefficient.

Medtronic, Inc. is sponsoring the MIRACLE EF study, a prospective, randomized, controlled, double-blinded, global multi-center, Cardiac Resynchronization Therapy (CRT) in Heart Failure (HF) clinical study. The purpose of this study is to evaluate market released CRT pacemaker (CRT-P) devices in symptomatic HF patients with less severe left ventricular systolic dysfunction, specifically patients with reduced left ventricular ejection fraction (LVEF) in the range of 36% to 50%. This study will support expansion of indications for CRT worldwide. The outcome of this study is expected to support modification of existing U.S. and Japanese labeling for Medtronic's implantable CRT-P devices and to provide further evidence to support changes to cardiology practice guidelines (ACC/AHA, ESC guidelines) regarding the use of CRT in patients with mild to moderate HF.

Following enrollment and the baseline assessment, eligible subjects will be implanted with a CRT-P system and randomized in a 2:1 fashion to either treatment (CRT-P ON) or control (CRT-P OFF) groups. Study subjects will be followed for a minimum of 24 months or until study closure, and will remain in their randomized groups until their 60 month visit or until the study is stopped, whichever comes first. The effectiveness of CRT-P in this population will be assessed using a composite endpoint of time to first event, with event defined as All-cause mortality or HF Event. To assess the safety of CRT-P in this population, the primary safety endpoint will measure freedom from system-related complications at 6 months post-implant.

Inclusion Criteria:

• Patient has diagnosis of chronic heart failure > 90 days in duration
• Has left ventricular ejection fraction (LVEF) between 36% and 50%, inclusive, as documented at baseline or within 30 days prior to enrollment
• Is either: (a) NYHA Class III at enrollment or at baseline OR (b) NYHA Class II at enrollment or at baseline, with a documented hospitalization for HF in the 12 months prior to enrollment OR (c) NYHA Class II at enrollment or at baseline, without a documented hospitalization for HF in the prior 12 months, but with BNP ≥250 pg/ml or NT-proBNP ≥1000 pg/ml
• Has documented left bundle branch block (LBBB) with QRS ≥130ms at baseline or within 30 days prior to enrollment.
• Is in sinus rhythm at time of enrollment or at the baseline visit.
• Has had no additions to or subtractions from non-diuretic heart failure medical therapy within 30 days prior to enrollment
• Is on maximum tolerated (guideline) dosages of medications in ACC/AHA guidelines for HF, Ischemic Heart Disease, Hypertension and AF as appropriate.
• Has signed and dated the study informed consent.
• Is able to receive a pectoral CRT-P implant.
• Is expected to remain available for follow-up visits.
• Is willing and able to comply with the Clinical Investigation Plan.

Exclusion Criteria:

• Requires permanent cardiac pacing.
• Indicated for implantable cardioverter defibrillator (ICD), such as for secondary prevention of prior sudden cardiac arrest, related to prior history of ventricular tachycardia and/or ventricular fibrillation.
• Less than 18 years of age, or under a higher minimum age requirement as defined by local law.
• Unstable angina or an acute MI within 40 days prior to enrollment.
• Coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within the 90 days prior to enrollment.
• Chronic (permanent) atrial arrhythmias. Chronic (permanent) atrial arrhythmias are defined as cases of long-standing atrial fibrillation (e.g., greater than 1 year) in which cardioversion has not been indicated or attempted.
• Cardioversion for atrial fibrillation within 30 days prior to enrollment.
• Treatable pericardial constraint within 30 days prior to enrollment.
• Restrictive (infiltrative) cardiomyopathies, such as amyloidosis, sarcoidosis, or hemochromatosis.
• Enrolled in a concurrent study, with the exception of a study-manager approved study that is strictly observational in nature and does not confound the results of this study (e.g. registries).
• Life expectancy of less than 24 months due to non-cardiac conditions.
• Pregnant, or of childbearing potential and not on a reliable form of birth control.
• CRT-P, pacemaker, ICD or CRT-D device implanted previously, or currently.
• Restrictive, hypertrophic, or reversible cardiomyopathy.
• Mechanical right heart valve.
• Primary valvular disease and is indicated for valve repair or replacement.
• Heart transplant, or is currently on a heart transplant list.
• Significant renal dysfunction, as manifested by serum creatinine level >2.5 mg/dl or ≥275 μmol/L or estimated glomerular filtration rate (GFR) ≤30 mL/min/1.73 m2, which is documented within the 30 days prior to enrollment or at baseline.
• Significant hepatic dysfunction, as evidenced by a hepatic function panel (serum) > 3 times upper limit of normal, which is documented within the 30 days prior to enrollment or at baseline.
• Chronic or treatment-resistant severe anemia (hemoglobin <10.0 g/dL), which is documented within the 30 days prior to enrollment or at baseline.
• On intravenous inotropic drug therapy.