Clinical trial NCT01735916: MIRACLE EF Clinical Study
Official title: MIRACLE EF Clinical Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Congestive Heart Failure
Left Bundle Branch Block
Systolic Heart Failure
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2012-11-28
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mortality or Heart Failure Morbidity
timeFrame: From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
measure: System-related Complication
timeFrame: From the date of implant to the date of 6 month follow-up visit
Secondary outcomes:
measure: Mortality
timeFrame: From date of randomization to date of death, for a minimum of 24 months and up to 60 months
measure: Mortality or Heart Failure Morbidity or Worsening Systolic Function
timeFrame: From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
measure: Recurrent HF Events
timeFrame: From date of randomization to date of event, assessed for a minimum of 24 months and up to 60 months
measure: Quality of Life (QoL)
timeFrame: Assessed from baseline visit to 24-month follow-up visit
measure: Reverse Remodeling by Echocardiography
timeFrame: Assessed from baseline visit to 24-month follow-up visit
Other outcomes:
Locations:
city: Concord
country: United States
facility: John Muir Medical Center, Cor Cardiovascular Specialists, John Muir Medical Center (Concord), John Muir Cardiovascular Institute, Contra Costa Cardiology
state: California
city: La Jolla
country: United States
facility: Scripps Clinic Torrey Pines, Scripps Green Hospital
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Desert Cardiology Center, Eisenhower Medical Center Hospital
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Medical Center
state: California
city: Colorado Springs
country: United States
facility: Colorado Health Medical Group, Memorial Hospital Colorado Springs
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Bradenton
country: United States
facility: Bradenton Cardiology, Manatee Memorial Hospital
state: Florida
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates / Century Research Associates, Holmes Regional Medical Center Hospital
state: Florida
city: Miami
country: United States
facility: Aventura Hospital and Medical Center, Hospital Corporation of America (Aventura), Hospital Corporation of America (Miami)
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Marietta
country: United States
facility: WellStar Cobb Hospital, WellStar Kennestone Hospital
state: Georgia
city: Elmhurst
country: United States
facility: Advocate Medical Group, Midwest Heart Specialists (Elmhurst), Elmhurst Memorial Hospital
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative (Springfield IL), Prairie Education Research Consultants, St. John's Hospital (Springfield IL)
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic PC
state: Iowa
city: Davenport
country: United States
facility: Cardiovascular Medicine PC (Davenport IA), Trinity (Rock Island), Midwest Cardiovascular Research Foundation, Trinity Bettendorf Hospital
state: Iowa
city: Overland Park
country: United States
facility: Midwest Cardiology Associates PA, Menorah Medical Center, Centerpoint Medical Center, Overland Park Regional Medical Center Hospital
state: Kansas
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute, McLaren Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Maplewood
country: United States
facility: HealthEast HeartCare Clinic at Saint John's
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: The Cardiovascular Center, University of Minnesota Medical Center Fairview
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Heart and Vascular Institute, North Memorial Medical Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart & Vascular Center
state: Minnesota
city: Saint Paul
country: United States
facility: Minneapolis Heart Institute Foundation, Mercy Hospital (Coon Rapids MN), Unity Hospital, United Hospital, Abbott Northwestern Hospital
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cardiovascular Specialists, Boone Hospital Center
state: Missouri
city: Kansas City
country: United States
facility: Cardiovascular Consultants, P.C., Saint Luke's Hospital, Mid America Heart Institute (MAHI)
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Heart and Vascular Clinic, Mercy Hospital St. Louis
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute Cardiology, Duplicate Glacier View Research Institute Hospital
state: Montana
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute PA
state: New Mexico
city: Buffalo
country: United States
facility: Buffalo Heart Group LLP, Buffalo Heart Group LLC-Cheektowaga, Mercy Hospital of Buffalo
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Islandia Clinic, Stony Brook Hauppauge, Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center, Duke University Medical Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Cardiology Services, FirstHealth Moore Regional Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Medical Center, Novant Clinical Research Institute
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center
state: North Dakota
city: Cincinnati
country: United States
facility: Lindner Research Center, The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, Ohio State University Medical Center The Richard M Ross Heart Hospital
state: Ohio
city: Fairfield
country: United States
facility: Mercy Hospital Fairfield, Mercy Hospital Anderson, The Jewish Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Corvallis
country: United States
facility: Samaritan Health Services
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Newtown
country: United States
facility: Mercer Bucks Cardiology, Saint Mary Medical Center, Arrhythmia Institute Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center UPMC Presbyterian
state: Pennsylvania
city: York
country: United States
facility: Cardiac Diagnostic Associates, York Hospital
state: Pennsylvania
city: Florence
country: United States
facility: Pee Dee Cardiology, McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Arrhythmia Consultants (Greenville SC), Greenville Memorial Hospital
state: South Carolina
city: Spartanburg
country: United States
facility: Cardiology Consultants PA, Spartanburg Regional Hospital
state: South Carolina
city: Kingsport
country: United States
facility: Wellmont CVA Heart Institute, Wellmont Holston Valley Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Centennial Heart Cardiovascular Consultants LLC
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Research Institute LLC, Baptist Hospital
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Heart Group, Northwest Texas Hospital
state: Texas
city: Amarillo
country: United States
facility: Cardiology Center of Amarillo, Northwest Texas Hospital
state: Texas
city: Dallas
country: United States
facility: HeartPlace Cardiology Research, Baylor Heart & Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Methodist DeBakey Cardiology Associates, The Methodist Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Research Institute (Plano TX), Legacy Heart Center
state: Texas
city: Temple
country: United States
facility: Scott & White Hospital
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia (UVA) Medical Center
state: Virginia
city: Lynchburg
country: United States
facility: Centra Medical Group Stroobants Cardiovascular Center, Centra Lynchburg General Hospital
state: Virginia
city: Mechanicsville
country: United States
facility: Richmond Cardiology Associates, Bon Secours Memorial Regional Medical Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cardiovascular Specialist, Sentara Williamsburg Regional Medical Center, Sentara Norfolk General Hospital, Sentara Virginia Beach General Hospital
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center, University of Washington (UW) Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora Cardiovascular Services, Aurora Sinai Medical Center, Aurora Saint Luke's Medical Center
state: Wisconsin
city: Haryana
country: India
facility: Medanta-The Medicity
city: Tyumen
country: Russian Federation
facility: Tyumen Cardiology Center
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals of Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Cecilia Linde, MD PhD
role: STUDY_CHAIR
References: