Evaluate Safety and Efficacy of the OPTIMIZER® System in Subjects With Moderate-to-Severe Heart Failure: FIX-HF-5C (FIX-HF-5C)

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

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.

Study Overview

• Status: Completed
• Conditions: NYHA Class III Heart Failure; NYHA Class IV Heart Failure
• Intervention / Treatment: Device: Optimizer System; Other: No intervention: Optimal medical therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 15030
    • Na Homolce Hospital
• Germany
  • Bad Bevensen, Germany, 29549
    • Herz- und Gefässzentrum Bad Bevensen
  • Berlin, Germany, 12203
    • Charité Berlin - Campus Benjamin Franklin
  • Berlin, Germany, 13353
    • Charité Campus-Virchow-Klinikum
  • Hamburg, Germany, 20099
    • Asklepios Klinik St. Georg
  • Hamburg, Germany, 20246
    • UKE - Universitäres Herzzentrum GmbH
  • Mannheim, Germany, 68167
    • Universitätsmedizin Mannheim
  • München, Germany, 81377
    • Klinikum der Univ. München - Grosshadern
  • Göttingen
    • Hanover, Göttingen, Germany, 37075
      • Universitatsmedizin Gottingen
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • Universitätsklinikum Essen
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Cardiovascular Consultants
    • Mesa, Arizona, United States, 85206
      • Chan Heart Rhythm Institute
    • Mesa, Arizona, United States, 85206
      • CardioVascular Associates of Mesa
    • Phoenix, Arizona, United States, 85013
      • Arizona Heart & Rhythm Center
    • Tucson, Arizona, United States, 85724
      • University of Arizona Sarver Heart Center
    • Tucson, Arizona, United States, 85712
      • Pima Heart
  • California
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale - New Haven Hospital
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Tampa, Florida, United States, 33613
      • Florida Hospital - Pepin Heart Institute
  • Illinois
    • Naperville, Illinois, United States, 60540
      • Advocate Medical Group - Midwest Heart Foundation
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Brighton, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center - Cardiovascular Institute
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Nebraska Heart Institute
    • Lincoln, Nebraska, United States, 69506
      • Bryan Heart LGH
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
    • Tyler, Texas, United States, 75701
      • Trinity Clinic
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart & Vascular Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; The treatment group receives the OPTIMIZER System implant and continues with optimal heart failure medical therapy.	Device: Optimizer System; The OPTIMIZER System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.; Other Names: CCM therapy
Other: Control; The Control group will not receive the OPTIMIZER System and will continue with optimal heart failure medical therapy.	Other: No intervention: Optimal medical therapy; The control group receives optimal medical therapy only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak VO2	Exercise tolerance quantified by peak VO2 measured with cardiopulmonary exercise stress testing (CPX) and evaluated by a blinded core lab.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Living With Heart Failure (MLWHF) Questionnaire	Change in quality of life at 24 weeks compared to baseline, as assessed by the Minnesota Living with Heart Failure (MLWHF) Questionnaire. The MLWHFQ score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of lif	24 weeks
Peak VO2 With Respiratory Exchange Ratio (RER)	Peak VO2 with change in respiratory exchange ratio (RER) included as a covariate, as measured by a blinded core lab.	24 weeks
NYHA	Heart failure class, as assessed by the New York Heart Association (NYHA) classification.	24 weeks
Peak VO2 With a Peak RER of ≥1.05	Peak VO2 in an analysis that only includes tests with a peak RER of ≥1.05.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute Hall Walk	Distance walked in 6 minutes	24 weeks
VE/VCO2	VE/VCO2 measured during cardiopulmonary stress testing (CPX) and evaluated by a blinded core lab.	24 weeks

Collaborators and Investigators

• Sponsor: Impulse Dynamics
• Investigators: Study Director: Daniel Burkhoff, MD, PhD, Impulse Dynamics

Publications and helpful links

General Publications

• 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. Erratum In: JACC Heart Fail. 2023 Jan;11(1):132.
• 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. Erratum In: Am Heart J. 2011 Jun;161(6):1220.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Impulse Dynamics Website

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 19, 2019
• Study Completion (Actual): March 19, 2019

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): September 17, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Heart Failure; CHF; Congestive Heart Failure; CCM; Cardiac contractility modulation; Chronic heart disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CP OPT2009-009; G030099 (Other Identifier: FDA)