MIRACLE EF Clinical Study

Congestive Heart Failure Clinical Trial

— MIRACLE EF  

Official title:

MIRACLE EF Clinical Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01735916
• Other study ID #: MIRACLE EF
• Status: Terminated
• Phase: N/A
• First received: November 15, 2012
• Last updated: October 5, 2017
• Start date: December 2012
• Est. completion date: March 2014

Study information

• Verified date: October 2017
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bundle-Branch Block
• Congestive Heart Failure
• Heart Failure
• Heart Failure, Systolic
• Left Bundle Branch Block
• Systolic Heart Failure

Intervention

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.
• CRT-P OFF
Device programmed to minimal pacing at 40 beats/minute. Device and arrhythmia diagnostics may remain enabled.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure

Countries where clinical trial is conducted

United States,  India,  Russian Federation,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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