Clinical trial NCT00112125: Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects With Heart Failure: FIX-HF-5
Official title: Evaluation of the Safety and Efficacy of the OPTIMIZER System With Active Fixation Leads in Subjects With Heart Failure Resulting From Systolic Dysfunction: FIX-HF-5
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure, Congestive
Keywords: cardiac contractility modulation
heart failure
cardiopulmonary exercise test
chronic heart disease
Lead sponsor: Impulse Dynamics
Sponsor class: INDUSTRY
First posted: 2005-05-30
Enrollment: 428
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 purpose of this study is to determine whether treatment with the OPTIMIZER System is safe and effective in patients with moderate to severe heart failure symptoms.

Detailed description: IMPULSE Dynamics' FIX HF 5 US Study is a prospective, multi-center, 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/IV heart failure. The study will involve the recruitment of approximately 420 subjects at a total of up to 50 sites nationwide.

Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomized to receive the OPTIMIZER™ System or to a control group. All subjects randomized will be followed for 1 year and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive optimal medical therapy for the treatment of their heart failure.

The primary efficacy assessment consists of a change in exercise tolerance measured by cardiopulmonary exercise testing at baseline and 6 months. Safety variables, such as the rate and cause of hospitalizations or death, shall be collected in both groups and shall be compared at 12 months.

Eligibility criteria: Inclusion Criteria:

* Subjects who are 18 years of age or older
* Subjects who are either male or female
* Subjects who have a baseline ejection fraction of 35% or less by echocardiography.
* 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 patient is intolerant) and are in New York Heart Association functional Class III or IV at the time of enrollment.
* Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting 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.
* Subjects who, in the opinion of the Principle Investigator (based on the current guidelines for clinical practice), have a clinical indication for an implanted cardiac defibrillator (ICD) 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.
* Subjects who are willing and able to return for all follow-up visits.

Exclusion Criteria:

* Subjects whose baseline VO2,max is \<9 ml 02/min/kg.
* Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.
* 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 electrocardiography (ECG) changes during exercise testing performed during baseline evaluation.
* Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment.
* Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 premature ventricular complexes (PVCs) per 24 hours on baseline Holter monitoring.
* Subjects who have chronic atrial fibrillation or chronic atrial flutter or those cardioverted within 30 days of enrollment.
* Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease \[COPD\], peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to participate in a 6-minute walk or a cardiopulmonary stress test.
* Subjects who are scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
* Subjects who have a biventricular pacing system or who have an accepted indication for such a device.
* Subjects who have had a myocardial infarction within 90 days of enrollment.
* Subjects who have mechanical tricuspid or aortic valves.
* Subjects who have a prior heart transplant.
* Subjects who are participating in another experimental protocol.
* Subjects who are unable to provide informed consent.

Primary outcomes:
measure: Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT)
timeFrame: 24 weeks
measure: Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations
timeFrame: 50-weeks
Secondary outcomes:
measure: Peak VO2
timeFrame: 24 weeks
measure: New York Heart Association (NYHA) Functional Classification
timeFrame: 24 weeks
measure: Minnesota Living With Heart Failure (MLWHF) Questionnaire
timeFrame: 24 weeks
measure: Six Minute Hall Walk (6MW) Test
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Orangeburg
country: United States
facility: Impulse Dynamics
state: New York
Study officials:
affiliation: Impulse Dynamics
name: Dan Burkhoff, M.D, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Burkhoff D, Shemer I, Felzen B, Shimizu J, Mika Y, Dickstein M, Prutchi D, Darvish N, Ben-Haim SA. Electric currents applied during the refractory period can modulate cardiac contractility in vitro and in vivo. Heart Fail Rev. 2001 Jan;6(1):27-34. doi: 10.1023/a:1009851107189. No abstract available.
citation: Ellison K. Nonexcitatory stimulation: 2002: a pace odyssey. J Cardiovasc Electrophysiol. 2002 Jul;13(7):696-7. doi: 10.1046/j.1540-8167.2002.00696.x. No abstract available.
citation: Marrouche NF, Pavia SV, Zhuang S, Kim YJ, Tabata T, Wallick D, Saad E, Abdul-Karim A, Schweikert R, Saliba W, Tchou P, Natale A. Nonexcitatory stimulus delivery improves left ventricular function in hearts with left bundle branch block. J Cardiovasc Electrophysiol. 2002 Jul;13(7):691-5. doi: 10.1046/j.1540-8167.2002.00691.x.
citation: Mohri S, He KL, Dickstein M, Mika Y, Shimizu J, Shemer I, Yi GH, Wang J, Ben-Haim S, Burkhoff D. Cardiac contractility modulation by electric currents applied during the refractory period. Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1642-7. doi: 10.1152/ajpheart.00959.2001.
citation: Morita H, Suzuki G, Haddad W, Mika Y, Tanhehco EJ, Sharov VG, Goldstein S, Ben-Haim S, Sabbah HN. Cardiac contractility modulation with nonexcitatory electric signals improves left ventricular function in dogs with chronic heart failure. J Card Fail. 2003 Feb;9(1):69-75. doi: 10.1054/jcaf.2003.8.
citation: Mohri S, Shimizu J, Mika Y, Shemer I, Wang J, Ben-Haim S, Burkhoff D. Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart. Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1119-23. doi: 10.1152/ajpheart.00378.2002. Epub 2002 Nov 21.
citation: Sabbah HN, Haddad W, Mika Y, Nass O, Aviv R, Sharov VG, Maltsev V, Felzen B, Undrovinas AI, Goldstein S, Darvish N, Ben-Haim SA. Cardiac contractility modulation with the impulse dynamics signal: studies in dogs with chronic heart failure. Heart Fail Rev. 2001 Jan;6(1):45-53. doi: 10.1023/a:1009855208097.
citation: Pappone C, Rosanio S, Burkhoff D, Mika Y, Vicedomini G, Augello G, Shemer I, Prutchi D, Haddad W, Aviv R, Snir Y, Kronzon I, Alfieri O, Ben-Haim SA. Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002 Dec 15;90(12):1307-13. doi: 10.1016/s0002-9149(02)02868-0.
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.