MIRACLE EF Clinical Study (MIRACLE EF)

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.

Study Overview

• Status: Terminated
• Conditions: Congestive Heart Failure; Systolic Heart Failure; Left Bundle Branch Block
• Intervention / Treatment: Device: CRT-P Implant; Device: CRT-P OFF

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Haryana, India, 122041
    • Medanta-The Medicity
• Russian Federation
  • Tyumen, Russian Federation, 625026
    • Tyumen Cardiology Center
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals of Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
• United States
  • California
    • Concord, California, United States, 94520
      • John Muir Medical Center, Cor Cardiovascular Specialists, John Muir Medical Center (Concord), John Muir Cardiovascular Institute, Contra Costa Cardiology
    • La Jolla, California, United States, 92037
      • Scripps Clinic Torrey Pines, Scripps Green Hospital
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Desert Cardiology Center, Eisenhower Medical Center Hospital
    • Thousand Oaks, California, United States, 91360
      • Los Robles Medical Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado Health Medical Group, Memorial Hospital Colorado Springs
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
  • Florida
    • Bradenton, Florida, United States, 34205
      • Bradenton Cardiology, Manatee Memorial Hospital
    • Melbourne, Florida, United States, 32901
      • Melbourne Internal Medicine Associates / Century Research Associates, Holmes Regional Medical Center Hospital
    • Miami, Florida, United States, 33137
      • Aventura Hospital and Medical Center, Hospital Corporation of America (Aventura), Hospital Corporation of America (Miami)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Marietta, Georgia, United States, 30060
      • WellStar Cobb Hospital, WellStar Kennestone Hospital
  • Illinois
    • Elmhurst, Illinois, United States, 60126
      • Advocate Medical Group, Midwest Heart Specialists (Elmhurst), Elmhurst Memorial Hospital
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
    • Springfield, Illinois, United States, 62701
      • Prairie Education and Research Cooperative (Springfield IL), Prairie Education Research Consultants, St. John's Hospital (Springfield IL)
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC
    • Davenport, Iowa, United States, 52803
      • Cardiovascular Medicine PC (Davenport IA), Trinity (Rock Island), Midwest Cardiovascular Research Foundation, Trinity Bettendorf Hospital
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Midwest Cardiology Associates PA, Menorah Medical Center, Centerpoint Medical Center, Overland Park Regional Medical Center Hospital
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Sparrow Clinical Research Institute, McLaren Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Maplewood, Minnesota, United States, 55109
      • HealthEast HeartCare Clinic at Saint John's
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Minneapolis, Minnesota, United States, 55455
      • The Cardiovascular Center, University of Minnesota Medical Center Fairview
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Heart and Vascular Institute, North Memorial Medical Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Heart & Vascular Center
    • Saint Paul, Minnesota, United States, 55102
      • Minneapolis Heart Institute Foundation, Mercy Hospital (Coon Rapids MN), Unity Hospital, United Hospital, Abbott Northwestern Hospital
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cardiovascular Specialists, Boone Hospital Center
    • Kansas City, Missouri, United States, 64111
      • Cardiovascular Consultants, P.C., Saint Luke's Hospital, Mid America Heart Institute (MAHI)
    • Saint Louis, Missouri, United States, 63141
      • Mercy Heart and Vascular Clinic, Mercy Hospital St. Louis
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Research Institute Cardiology, Duplicate Glacier View Research Institute Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute PA
  • New York
    • Buffalo, New York, United States, 14215
      • Buffalo Heart Group LLP, Buffalo Heart Group LLC-Cheektowaga, Mercy Hospital of Buffalo
    • Stony Brook, New York, United States, 11794
      • Stony Brook Islandia Clinic, Stony Brook Hauppauge, Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center (DUMC)
    • Durham, North Carolina, United States, 27710
      • Durham VA medical Center, Duke University Medical Center
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth Cardiology Services, FirstHealth Moore Regional Hospital
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Medical Center, Novant Clinical Research Institute
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Sanford Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Lindner Research Center, The Christ Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University, Ohio State University Medical Center The Richard M Ross Heart Hospital
    • Fairfield, Ohio, United States, 45014
      • Mercy Hospital Fairfield, Mercy Hospital Anderson, The Jewish Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Samaritan Health Services
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • LeHigh Valley Hospital
    • Newtown, Pennsylvania, United States, 18940
      • Mercer Bucks Cardiology, Saint Mary Medical Center, Arrhythmia Institute Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center UPMC Presbyterian
    • York, Pennsylvania, United States, 17405
      • Cardiac Diagnostic Associates, York Hospital
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • Pee Dee Cardiology, McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29605
      • Arrhythmia Consultants (Greenville SC), Greenville Memorial Hospital
    • Spartanburg, South Carolina, United States, 29303
      • Cardiology Consultants PA, Spartanburg Regional Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont CVA Heart Institute, Wellmont Holston Valley Medical Center
    • Nashville, Tennessee, United States, 37203
      • Centennial Heart Cardiovascular Consultants LLC
    • Nashville, Tennessee, United States, 37205
      • Saint Thomas Research Institute LLC, Baptist Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Heart Group, Northwest Texas Hospital
    • Amarillo, Texas, United States, 79106
      • Cardiology Center of Amarillo, Northwest Texas Hospital
    • Dallas, Texas, United States, 75226
      • HeartPlace Cardiology Research, Baylor Heart & Vascular Hospital
    • Houston, Texas, United States, 77030
      • Methodist DeBakey Cardiology Associates, The Methodist Hospital
    • Plano, Texas, United States, 75204
      • Baylor Research Institute (Plano TX), Legacy Heart Center
    • Temple, Texas, United States, 76508
      • Scott & White Hospital
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Fletcher Allen Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia (UVA) Medical Center
    • Lynchburg, Virginia, United States, 24501
      • Centra Medical Group Stroobants Cardiovascular Center, Centra Lynchburg General Hospital
    • Mechanicsville, Virginia, United States, 23116
      • Richmond Cardiology Associates, Bon Secours Memorial Regional Medical Center
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Specialist, Sentara Williamsburg Regional Medical Center, Sentara Norfolk General Hospital, Sentara Virginia Beach General Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • Harborview Medical Center, University of Washington (UW) Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Cardiovascular Services, Aurora Sinai Medical Center, Aurora Saint Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CRT-P ON; CRT-P Implant CRT-P ON	Device: CRT-P Implant; The Medtronic Consulta CRT-P (models C3TR01, C4TR011) dual chamber implantable pacemaker with cardiac resynchronization therapy (CRT-P) is a multi-programmable cardiac device that monitors and regulates the patient's heart rate by providing single or dual chamber rate-responsive bradycardia pacing, and sequential biventricular pacing. The device senses the electrical activity of the patient's heart using the electrodes of the implanted atrial and right ventricular leads. It then analyzes the heart rhythm based on selectable detection parameters. The device responds to bradyarrhythmias by providing bradycardia pacing therapy. Simultaneous or sequential biventricular pacing is used to provide patients with cardiac resynchronization therapy. The device also provides diagnostic and monitoring information that assists with system evaluation and patient care.; Other Names: Cardiac Resynchronization Therapy Pacemaker (CRT-P); Consulta CRT-P; C4TR01
Placebo Comparator: CRT-P OFF; CRT-P Implant CRT-P OFF	Device: CRT-P Implant; The Medtronic Consulta CRT-P (models C3TR01, C4TR011) dual chamber implantable pacemaker with cardiac resynchronization therapy (CRT-P) is a multi-programmable cardiac device that monitors and regulates the patient's heart rate by providing single or dual chamber rate-responsive bradycardia pacing, and sequential biventricular pacing. The device senses the electrical activity of the patient's heart using the electrodes of the implanted atrial and right ventricular leads. It then analyzes the heart rhythm based on selectable detection parameters. The device responds to bradyarrhythmias by providing bradycardia pacing therapy. Simultaneous or sequential biventricular pacing is used to provide patients with cardiac resynchronization therapy. The device also provides diagnostic and monitoring information that assists with system evaluation and patient care.; Other Names: Cardiac Resynchronization Therapy Pacemaker (CRT-P); Consulta CRT-P; C4TR01; Device: CRT-P OFF; Device programmed to minimal pacing at 40 beats/minute. Device and arrhythmia diagnostics may remain enabled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality or Heart Failure Morbidity	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	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
System-related Complication	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	From the date of implant to the date of 6 month follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Time to death between the study groups Note: No endpoints were reached, so this objective was not analyzed	From date of randomization to date of death, for a minimum of 24 months and up to 60 months
Mortality or Heart Failure Morbidity or Worsening Systolic Function	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	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
Recurrent HF Events	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	From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
Quality of Life (QoL)	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	Assessed from baseline visit to 24-month follow-up visit
Reverse Remodeling by Echocardiography	The change in LVEF between study groups. Note: No subjects completed 24 months of follow-up, so this objective could not be analyzed.	Assessed from baseline visit to 24-month follow-up visit

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Study Chair: Cecilia Linde, MD PhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: November 15, 2012
• First Submitted That Met QC Criteria: November 21, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 5, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Heart Failure; Bundle-Branch Block; Heart Failure, Systolic
• Other Study ID Numbers: MIRACLE EF