MIRACLE EF Clinical Study

Not Applicable

Terminated

Conditions: Systolic Heart Failure
Congestive Heart Failure
Left Bundle Branch Block

Interventions: Device: CRT-P Implant
Device: CRT-P OFF

Registration Number: NCT01735916

Lead Sponsor: Medtronic Cardiac Rhythm and Heart Failure

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 44

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRT-P OFF	CRT-P Implant	CRT-P Implant CRT-P OFF
CRT-P OFF	CRT-P OFF	CRT-P Implant CRT-P OFF
CRT-P ON	CRT-P Implant	CRT-P Implant CRT-P ON

Primary Outcome Measures

Name	Time	Method
Mortality or Heart Failure Morbidity	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months	Primary Efficacy Endpoint: The time to first event, with event defined as: * All-cause mortality, or * HF Event, defined as either: * Inpatient hospitalization for HF, or * Outpatient event requiring invasive clinical intervention and management for HF (i.e. IV diuretics, ultrafiltration, or equivalent) and overnight stay Note: No endpoints were reached, so this objective was not analyzed
System-related Complication	From the date of implant to the date of 6 month follow-up visit	Primary Safety Endpoint: Time to first system-related complication in subjects with a successful implant. Note: Because of the small number of subjects, number of complications was noted between arms and a time to event analysis was not performed. Complication is defined as: An adverse event that results in death, involves any termination of significant device function, or requires an invasive intervention

Secondary Outcome Measures

Name	Time	Method
Mortality	From date of randomization to date of death, for a minimum of 24 months and up to 60 months	Time to death between the study groups Note: No endpoints were reached, so this objective was not analyzed
Mortality or Heart Failure Morbidity or Worsening Systolic Function	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months	Secondary Composite Efficacy Endpoint: The time to first event, with event defined as: * All-cause mortality * HF Event, defined as either: * Inpatient hospitalization for HF, or * Outpatient event requiring invasive clinical intervention and management for HF (i.e. IV diuretics, ultrafiltration, or equivalent) and overnight stay, or * Worsening systolic function meeting an ICD/CRT-D indication, defined as: * A drop in LVEF to 35% or below, with an absolute decrease of greater than or equal to 10%, after maximum tolerated doses of guideline HF medications have been established Note: No endpoints were reached, so this objective was not analyzed
Recurrent HF Events	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months	The frequency of HF events between the study groups Note: No endpoints were reached, so this objective was not analyzed - HF Event, defined as either: * Inpatient hospitalization for HF, or * Outpatient event requiring invasive clinical intervention and management for HF (i.e. IV diuretics, ultrafiltration, or equivalent) and overnight stay
Quality of Life (QoL)	Assessed from baseline visit to 24-month follow-up visit	The quality of life between study groups and the change in quality of life over time between study groups using clinically accepted quality of life measures. Note: No subjects completed 24 months of follow-up, so this objective could not be analyzed. Two QOL questionnaires were used in the study. EQ-5D: scores typically range from 0-1, where higher scores reflect better quality of life KCCQ: scores range from 0-100, where higher scores reflect better quality of life
Reverse Remodeling by Echocardiography	Assessed from baseline visit to 24-month follow-up visit	The change in LVEF between study groups. Note: No subjects completed 24 months of follow-up, so this objective could not be analyzed.

Trial Locations

Locations (73): Eisenhower Desert Cardiology Center, Eisenhower Medical Center Hospital
🇺🇸
Rancho Mirage, California, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Melbourne Internal Medicine Associates / Century Research Associates, Holmes Regional Medical Center Hospital
🇺🇸
Melbourne, Florida, United States
Advocate Christ Medical Center
🇺🇸
Oak Lawn, Illinois, United States
Midwest Cardiology Associates PA, Menorah Medical Center, Centerpoint Medical Center, Overland Park Regional Medical Center Hospital
🇺🇸
Overland Park, Kansas, United States
Lahey Hospital & Medical Center
🇺🇸
Burlington, Massachusetts, United States
Cardiac Diagnostic Associates, York Hospital
🇺🇸
York, Pennsylvania, United States
Cardiology Consultants PA, Spartanburg Regional Hospital
🇺🇸
Spartanburg, South Carolina, United States
Fletcher Allen Medical Center
🇺🇸
Burlington, Vermont, United States
Aventura Hospital and Medical Center, Hospital Corporation of America (Aventura), Hospital Corporation of America (Miami)
🇺🇸
Miami, Florida, United States
The Cardiovascular Center, University of Minnesota Medical Center Fairview
🇺🇸
Minneapolis, Minnesota, United States
Duke University Medical Center (DUMC)
🇺🇸
Durham, North Carolina, United States
Los Robles Medical Center
🇺🇸
Thousand Oaks, California, United States
Colorado Health Medical Group, Memorial Hospital Colorado Springs
🇺🇸
Colorado Springs, Colorado, United States
VA Greater Los Angeles Healthcare System
🇺🇸
Los Angeles, California, United States
Scripps Clinic Torrey Pines, Scripps Green Hospital
🇺🇸
La Jolla, California, United States
John Muir Medical Center, Cor Cardiovascular Specialists, John Muir Medical Center (Concord), John Muir Cardiovascular Institute, Contra Costa Cardiology
🇺🇸
Concord, California, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Prairie Education and Research Cooperative (Springfield IL), Prairie Education Research Consultants, St. John's Hospital (Springfield IL)
🇺🇸
Springfield, Illinois, United States
McFarland Clinic PC
🇺🇸
Ames, Iowa, United States
Cardiovascular Medicine PC (Davenport IA), Trinity (Rock Island), Midwest Cardiovascular Research Foundation, Trinity Bettendorf Hospital
🇺🇸
Davenport, Iowa, United States
William Beaumont Hospital
🇺🇸
Royal Oak, Michigan, United States
Minneapolis Heart Institute Foundation
🇺🇸
Minneapolis, Minnesota, United States
CentraCare Heart & Vascular Center
🇺🇸
Saint Cloud, Minnesota, United States
Minneapolis Heart Institute Foundation, Mercy Hospital (Coon Rapids MN), Unity Hospital, United Hospital, Abbott Northwestern Hospital
🇺🇸
Saint Paul, Minnesota, United States
Missouri Cardiovascular Specialists, Boone Hospital Center
🇺🇸
Columbia, Missouri, United States
Mercy Heart and Vascular Clinic, Mercy Hospital St. Louis
🇺🇸
Saint Louis, Missouri, United States
Glacier View Research Institute Cardiology, Duplicate Glacier View Research Institute Hospital
🇺🇸
Kalispell, Montana, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
New Mexico Heart Institute PA
🇺🇸
Albuquerque, New Mexico, United States
Buffalo Heart Group LLP, Buffalo Heart Group LLC-Cheektowaga, Mercy Hospital of Buffalo
🇺🇸
Buffalo, New York, United States
Stony Brook Islandia Clinic, Stony Brook Hauppauge, Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Durham VA Medical Center, Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
FirstHealth Cardiology Services, FirstHealth Moore Regional Hospital
🇺🇸
Pinehurst, North Carolina, United States
Ohio State University, Ohio State University Medical Center The Richard M Ross Heart Hospital
🇺🇸
Columbus, Ohio, United States
Mercy Hospital Fairfield, Mercy Hospital Anderson, The Jewish Hospital
🇺🇸
Fairfield, Ohio, United States
Samaritan Health Services
🇺🇸
Corvallis, Oregon, United States
Richmond Cardiology Associates, Bon Secours Memorial Regional Medical Center
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Mechanicsville, Virginia, United States
Scott & White Hospital
🇺🇸
Temple, Texas, United States
Centra Medical Group Stroobants Cardiovascular Center, Centra Lynchburg General Hospital
🇺🇸
Lynchburg, Virginia, United States
Sentara Cardiovascular Specialist, Sentara Williamsburg Regional Medical Center, Sentara Norfolk General Hospital, Sentara Virginia Beach General Hospital
🇺🇸
Norfolk, Virginia, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Saint Thomas Research Institute LLC, Baptist Hospital
🇺🇸
Nashville, Tennessee, United States
Centennial Heart Cardiovascular Consultants LLC
🇺🇸
Nashville, Tennessee, United States
Wellmont CVA Heart Institute, Wellmont Holston Valley Medical Center
🇺🇸
Kingsport, Tennessee, United States
Bradenton Cardiology, Manatee Memorial Hospital
🇺🇸
Bradenton, Florida, United States
WellStar Cobb Hospital, WellStar Kennestone Hospital
🇺🇸
Marietta, Georgia, United States
Advocate Medical Group, Midwest Heart Specialists (Elmhurst), Elmhurst Memorial Hospital
🇺🇸
Elmhurst, Illinois, United States
HealthEast HeartCare Clinic at Saint John's
🇺🇸
Maplewood, Minnesota, United States
North Memorial Heart and Vascular Institute, North Memorial Medical Center
🇺🇸
Robbinsdale, Minnesota, United States
Mercer Bucks Cardiology, Saint Mary Medical Center, Arrhythmia Institute Hospital
🇺🇸
Newtown, Pennsylvania, United States
Pee Dee Cardiology, McLeod Regional Medical Center
🇺🇸
Florence, South Carolina, United States
Sanford Medical Center
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Fargo, North Dakota, United States
Lindner Research Center, The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Integris Baptist Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
Medanta-The Medicity
🇮🇳
Haryana, India
Amarillo Heart Group, Northwest Texas Hospital
🇺🇸
Amarillo, Texas, United States
Cardiology Center of Amarillo, Northwest Texas Hospital
🇺🇸
Amarillo, Texas, United States
HeartPlace Cardiology Research, Baylor Heart & Vascular Hospital
🇺🇸
Dallas, Texas, United States
Methodist DeBakey Cardiology Associates, The Methodist Hospital
🇺🇸
Houston, Texas, United States
Baylor Research Institute (Plano TX), Legacy Heart Center
🇺🇸
Plano, Texas, United States
University of Virginia (UVA) Medical Center
🇺🇸
Charlottesville, Virginia, United States
Karolinska University Hospital
🇸🇪
Stockholm, Sweden
University Hospitals of Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
🇬🇧
Birmingham, United Kingdom
Tyumen Cardiology Center
🇷🇺
Tyumen, Russian Federation
Sparrow Clinical Research Institute, McLaren Hospital
🇺🇸
Lansing, Michigan, United States
University of Pittsburgh Medical Center UPMC Presbyterian
🇺🇸
Pittsburgh, Pennsylvania, United States
Lehigh Valley Hospital
🇺🇸
Allentown, Pennsylvania, United States
Arrhythmia Consultants (Greenville SC), Greenville Memorial Hospital
🇺🇸
Greenville, South Carolina, United States
Harborview Medical Center, University of Washington (UW) Medical Center
🇺🇸
Seattle, Washington, United States
Forsyth Medical Center, Novant Clinical Research Institute
🇺🇸
Winston-Salem, North Carolina, United States
Aurora Cardiovascular Services, Aurora Sinai Medical Center, Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Cardiovascular Consultants, P.C., Saint Luke's Hospital, Mid America Heart Institute (MAHI)
🇺🇸
Kansas City, Missouri, United States