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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Heart Failure, Congestive

Intervention / Treatment
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* Device: OPTIMIZER System


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optimizer System + Optimal medical treatment<br>Optimizer System implanted and cardiac contractility modulation therapy activated. | Device: OPTIMIZER System<br> <br> |
| No Intervention: Optimal medical treatment<br>Treatment with optimal medical therapy only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak VO2 | Number of participants with improvement in peak VO2 measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if peak VO2 increases by ≥20% at 24 weeks compared to their respective baseline value. | 24 weeks | 
| New York Heart Association (NYHA) Functional Classification | Number of participants with improvement in heart failure symptoms as quantified by a blinded clinician using the New York Heart Association (NYHA) functional classification at 24 weeks compared to baseline. The NYHA Class ranges from I - IV, with a lower class indicating a better status. Note: An individual subject is considered a responder if the NYHA class decreases by ≥ 1 at 24 weeks compared to their respective baseline class. | 24 weeks | 
| Minnesota Living With Heart Failure (MLWHF) Questionnaire | Number of subjects will improvement 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 life. Note: An individual subject is considered a responder if the MLWHFQ score decreases by ≥10 points at 24 weeks compared to their respective baseline score. | 24 weeks | 
| Six Minute Hall Walk (6MW) Test | Number of subjects with improvement in exercise tolerance at 24 weeks compared to baseline, as assessed by the the six minute hall walk (6MW) test. Note: An individual subject is considered a responder with >40-meter increase in distance walked at 24 weeks compared to their respective baseline distance. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac contractility modulation, heart failure, cardiopulmonary exercise test, chronic heart disease