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

NYHA Class III Heart Failure Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381172
• Other study ID #: CP OPT2009-009
• Secondary ID: G030099
• Status: Completed
• Phase: N/A
• Start date: January 2011
• Est. completion date: March 19, 2019

Study information

• Verified date: August 2021
• Source: Impulse Dynamics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: March 19, 2019
• Est. primary completion date: March 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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 ß-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.

Related Conditions & MeSH terms

• Heart Failure
• NYHA Class III Heart Failure
• NYHA Class IV Heart Failure

Intervention

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:
• No intervention: Optimal medical therapy
The control group receives optimal medical therapy only.

Locations

Country	Name	City	State
Czechia	Na Homolce Hospital	Prague
Germany	Herz- und Gefässzentrum Bad Bevensen	Bad Bevensen
Germany	Charité Berlin - Campus Benjamin Franklin	Berlin
Germany	Charité Campus-Virchow-Klinikum	Berlin
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	ASKLEPIOS Klinik St. Georg	Hamburg
Germany	UKE - Universitäres Herzzentrum GmbH	Hamburg
Germany	Universitätsmedizin Göttingen	Hanover	Göttingen
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Klinikum der Univ. München - Grosshadern	München
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	St. Elizabeth's Medical Center	Brighton	Massachusetts
United States	The Lindner Center	Cincinnati	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Dallas VA Medical Center	Dallas	Texas
United States	Detroit Medical Center - Cardiovascular Institute	Detroit	Michigan
United States	Inova Heart & Vascular Institute	Falls Church	Virginia
United States	Stern Cardiovascular Foundation	Germantown	Tennessee
United States	Cardiovascular Consultants	Glendale	Arizona
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Bryan Heart LGH	Lincoln	Nebraska
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Cardiovascular Associates of Mesa	Mesa	Arizona
United States	Chan Heart Rhythm Institute	Mesa	Arizona
United States	Aurora Health Care	Milwaukee	Wisconsin
United States	Advocate Medical Group - Midwest Heart Foundation	Naperville	Illinois
United States	Yale - New Haven Hospital	New Haven	Connecticut
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Mt. Sinai Medical Center	New York	New York
United States	UMDNJ	Newark	New Jersey
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Florida Hospital	Orlando	Florida
United States	Arizona Heart & Rhythm Center	Phoenix	Arizona
United States	Guthrie Medical Group	Sayre	Pennsylvania
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	Florida Hospital - Pepin Heart Institute	Tampa	Florida
United States	Pima Heart	Tucson	Arizona
United States	University of Arizona Sarver Heart Center	Tucson	Arizona
United States	Trinity Clinic	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Impulse Dynamics

Countries where clinical trial is conducted

United States,  Czechia,  Germany, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. Erratum in: Am Heart J. 2011 Jun;161(6):1220. — View 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. Epub 2006 Jul 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	6 Minute Hall Walk	Distance walked in 6 minutes	24 weeks
Other	VE/VCO2	VE/VCO2 measured during cardiopulmonary stress testing (CPX) and evaluated by a blinded core lab.	24 weeks
Primary	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	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
Secondary	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
Secondary	NYHA	Heart failure class, as assessed by the New York Heart Association (NYHA) classification.	24 weeks
Secondary	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

External Links

•   Impulse Dynamics Website