Clinical trial NCT01381172: Evaluate Safety and Efficacy of the OPTIMIZER® System in Subjects With Moderate-to-Severe Heart Failure: FIX-HF-5C
Official title: Evaluation of the Safety and Efficacy of the OPTIMIZER® System in Subjects With Moderate-to-Severe Heart Failure With Ejection Fraction Between 25% and 45%: FIX-HF-5C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NYHA Class III Heart Failure
NYHA Class IV Heart Failure
Keywords: Heart Failure
Congestive Heart Failure
Chronic heart disease
Cardiac contractility modulation
CCM
CHF
Lead sponsor: Impulse Dynamics
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 160
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: The objective of this investigation is to evaluate the safety and effectiveness of the OPTIMIZER® System in subjects with medically refractory moderate-to-severe heart failure.

Detailed description: The Impulse Dynamics FIX-HF-5C Study is a prospective, multicenter, randomized study to evaluate the safety and efficacy of cardiac contractility modulation (CCM) signals delivered by the implantable OPTIMIZER System in patients with NYHA class III and IV heart failure and an ejection fraction 25-45%. The study will involve the recruitment of 160 subjects at a total of up to 60 sites.

Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomly assigned in a 1:1 ratio to either the OPTIMIZER System plus optimal medical therapy (OMT) or to a control group receiving OMT alone. All randomized subjects will be followed for 24 weeks and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive OMT for the treatment of their heart failure. Mortality will be reported out to 2 years.

Eligibility criteria: Inclusion Criteria:

1. Subjects who are 18 years of age or older
2. Subjects who are either male or female. Females of childbearing potential must be using a medically approved method of birth control and must agree to continue to use birth control throughout the study, or must be surgically sterilized (tubal ligation, hysterectomy) or post-menopausal for at least 1 year.
3. Condition

   1. Subjects who have a baseline ejection fraction greater than or equal to 25% and less than or equal to 45% by echocardiography determined by the echocardiography core laboratory.
   2. Subjects who have been treated for heart failure for at least 90 days (including treatment with a β-blocker for at least 90 days unless the subject is intolerant) and are in New York Heart Association functional Class III and IV at the time of enrollment.
   3. Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure according to the region- specific guideline recommendations. For patients with EF≤35%, this regimen shall consist of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and β-blocker. Stable is defined as no more than a 100% increase or 50% decrease in dose.
   4. Subjects who, in the opinion of the Principal Investigator (based on the current guidelines for clinical practice ), have a clinical indication for an implanted cardiac defibrillator (ICD, e.g., EF≤35%) and/or pacemaker, must have an existing device or agree to undergo implantation of such a device unless the patient refuses to undergo the implantation of such device for personal reasons.
   5. Subjects who are willing and able to return for all follow-up visits.

Exclusion Criteria:

1. Subjects whose baseline peak VO2 is \<9 or \>20 ml O2/min/kg.
2. Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.
3. Subjects who have clinically significant angina pectoris, consisting of angina during daily life (i.e., Canadian Cardiovascular Society Angina score of II or more), an episode of unstable angina within 30 days of enrollment, or angina and/or ECG changes during exercise testing performed during baseline evaluation.
4. Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment.
5. Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 PVCs per 24 hours on baseline Holter monitoring.
6. Subjects having a PR interval greater than 375 ms.
7. Subjects who have chronic (permanent or persistent) atrial fibrillation or atrial flutter or those cardioverted within 30 days of enrollment.
8. Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, COPD, peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to perform baseline stress testing.
9. Subjects who are scheduled for a CABG or a PTCA procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
10. Subjects who have a biventricular pacing system, an accepted indication for such a device, or a QRS width of 130ms or greater.
11. Subjects who have had a myocardial infarction within 90 days of enrollment.
12. Subjects who have mechanical tricuspid valve.
13. Subjects who have a prior heart transplant.
14. Subjects on dialysis.
15. Subjects who are participating in another experimental protocol.
16. Subjects who are unable to provide informed consent.

Primary outcomes:
measure: Peak VO2
timeFrame: 24 weeks
Secondary outcomes:
measure: Minnesota Living With Heart Failure (MLWHF) Questionnaire
timeFrame: 24 weeks
measure: Peak VO2 With Respiratory Exchange Ratio (RER)
timeFrame: 24 weeks
measure: NYHA
timeFrame: 24 weeks
measure: Peak VO2 With a Peak RER of ≥1.05
timeFrame: 24 weeks
Other outcomes:
measure: 6 Minute Hall Walk
timeFrame: 24 weeks
measure: VE/VCO2
timeFrame: 24 weeks
Locations:
city: Glendale
country: United States
facility: Cardiovascular Consultants
state: Arizona
city: Mesa
country: United States
facility: Cardiovascular Associates of Mesa
state: Arizona
city: Mesa
country: United States
facility: Chan Heart Rhythm Institute
state: Arizona
city: Phoenix
country: United States
facility: Arizona Heart & Rhythm Center
state: Arizona
city: Tucson
country: United States
facility: Pima Heart
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Sarver Heart Center
state: Arizona
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: New Haven
country: United States
facility: Yale - New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Tampa
country: United States
facility: Florida Hospital - Pepin Heart Institute
state: Florida
city: Naperville
country: United States
facility: Advocate Medical Group - Midwest Heart Foundation
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Takoma Park
country: United States
facility: Washington Adventist Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Brighton
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Detroit Medical Center - Cardiovascular Institute
state: Michigan
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Lincoln
country: United States
facility: Bryan Heart LGH
state: Nebraska
city: Newark
country: United States
facility: UMDNJ
state: New Jersey
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: The Lindner Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Sayre
country: United States
facility: Guthrie Medical Group
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Foundation
state: Tennessee
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Tyler
country: United States
facility: Trinity Clinic
state: Texas
city: Falls Church
country: United States
facility: Inova Heart & Vascular Institute
state: Virginia
city: Milwaukee
country: United States
facility: Aurora Health Care
state: Wisconsin
city: Prague
country: Czechia
facility: Na Homolce Hospital
city: Hanover
country: Germany
facility: Universitätsmedizin Göttingen
state: Göttingen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Bad Bevensen
country: Germany
facility: Herz- und Gefässzentrum Bad Bevensen
city: Berlin
country: Germany
facility: Charité Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité Campus-Virchow-Klinikum
city: Hamburg
country: Germany
facility: ASKLEPIOS Klinik St. Georg
city: Hamburg
country: Germany
facility: UKE - Universitäres Herzzentrum GmbH
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: München
country: Germany
facility: Klinikum der Univ. München - Grosshadern
Study officials:
affiliation: Impulse Dynamics
name: Daniel Burkhoff, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kadish A, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Abraham WT. A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. Am Heart J. 2011 Feb;161(2):329-337.e1-2. doi: 10.1016/j.ahj.2010.10.025.
citation: Abraham WT, Burkhoff D, Nademanee K, Carson P, Bourge R, Ellenbogen KA, Parides M, Kadish A; FIX-HF-5 Investigators and Coordinators. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics. Am Heart J. 2008 Oct;156(4):641-648.e1. doi: 10.1016/j.ahj.2008.05.019.
citation: Neelagaru SB, Sanchez JE, Lau SK, Greenberg SM, Raval NY, Worley S, Kalman J, Merliss AD, Krueger S, Wood M, Wish M, Burkhoff D, Nademanee K. Nonexcitatory, cardiac contractility modulation electrical impulses: feasibility study for advanced heart failure in patients with normal QRS duration. Heart Rhythm. 2006 Oct;3(10):1140-7. doi: 10.1016/j.hrthm.2006.06.031. Epub 2006 Jul 8.
citation: Abraham WT, Nademanee K, Volosin K, Krueger S, Neelagaru S, Raval N, Obel O, Weiner S, Wish M, Carson P, Ellenbogen K, Bourge R, Parides M, Chiacchierini RP, Goldsmith R, Goldstein S, Mika Y, Burkhoff D, Kadish A; FIX-HF-5 Investigators and Coordinators. Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. J Card Fail. 2011 Sep;17(9):710-7. doi: 10.1016/j.cardfail.2011.05.006. Epub 2011 Jun 22.
citation: Abraham WT, Lindenfeld J, Reddy VY, Hasenfuss G, Kuck KH, Boscardin J, Gibbons R, Burkhoff D; FIX-HF-5C Investigators and Coordinators. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with moderately reduced left ventricular ejection fraction and a narrow QRS duration: study rationale and design. J Card Fail. 2015 Jan;21(1):16-23. doi: 10.1016/j.cardfail.2014.09.011. Epub 2014 Oct 5.
citation: Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.