Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects With Heart Failure: FIX-HF-5

NCT00112125 | Completed Results DMC

• 2 other identifiers: #IDPT 2003-07-CFIX-HF-5
• Study Type: interventional
• Target: 428
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure, Congestive

Keywords

cardiac contractility modulation; heart failure; cardiopulmonary exercise test; chronic heart disease

Outcome Measures

Primary Outcomes (2)

• Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT)

  Number of participants with improvement in exercise tolerance at 24 weeks compared to baseline, as quantified by VO2 at ventilatory anerobic threshold (VAT) measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if VAT increases by ≥20% at 24 weeks compared to their respective baseline value.

  24 weeks

• Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations

  The proportion of patients experiencing a composite event of all-cause mortality and all-cause hospitalizations evaluated at 50-weeks

  50-weeks

Secondary Outcomes (4)

• Peak VO2

  24 weeks

• New York Heart Association (NYHA) Functional Classification

  24 weeks

• Minnesota Living With Heart Failure (MLWHF) Questionnaire

  24 weeks

• Six Minute Hall Walk (6MW) Test

  24 weeks

Study Arms (2)

Optimizer System + Optimal medical treatment

EXPERIMENTAL

Optimizer System implanted and cardiac contractility modulation therapy activated.

Device: OPTIMIZER System

Optimal medical treatment

NO INTERVENTION

Treatment with optimal medical therapy only.

Interventions

OPTIMIZER System DEVICE

Optimizer System + Optimal medical treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Impulse Dynamics: lead

Study Sites (1)

Impulse Dynamics

Orangeburg, New York, 10962, United States

Location

Related Publications (9)

• 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.

  PMID: 11248765 BACKGROUND

• 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.

  PMID: 12139295 BACKGROUND

• 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.

  PMID: 12139294 BACKGROUND

• 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.

  PMID: 11959626 BACKGROUND

• 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.

  PMID: 12612875 BACKGROUND

• 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.

  PMID: 12446280 BACKGROUND

• 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.

  PMID: 11248767 BACKGROUND

• 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.

  PMID: 12480039 BACKGROUND

• 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.

  PMID: 18926146 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

The primary endpoint was not validated for use in HF trials (VAT, responder analysis, responder = 20% increase). VAT was missing or indeterminant in 30% of subjects despite use of 2 blinded core labs. ITT analysis required 10 levels of imputation.

Results Point of Contact

• Title: Angela Stagg, Sr. Director, Clinical and Data Operations
• Organization: Impulse Dynamics (USA) Inc

angelas@impulse-dynamics.com

8453592389

Study Officials

• Dan Burkhoff, M.D, Ph.D.

  Impulse Dynamics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2005
• First Posted: May 30, 2005
• Study Start: February 1, 2005
• Primary Completion: March 19, 2019
• Study Completion: March 19, 2019
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2020-07

Locations

US (1)