Prospective Evaluation of Elastic Restraint to LESSen the Effects of Heart Failure (PEERLESS-HF) Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine if patients in the HeartNet Ventricular Support System with optimal medical and device therapy arm (Treatment group) show statistically significant improvement compared to patients in the optimal medical and device therapy alone arm (Control group) after 6 months of follow-up.

Detailed Description
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In the United States alone, more than five million people suffer from heart failure (CHF) and an estimated 400,000 to 700,000 new cases are diagnosed each year. Caused by a variety of cardiac conditions, systolic heart failire (HF) is the end-stage of heart disease where the heart is failing as a pump. Once diagnosed with the disease, less than 50% of the patients live for five years, and less than 25% survive for more than ten years. The number of deaths in the United States from this condition has more than doubled since 1979, averaging more than 250,000 annually. Paracor Medical, Inc. has developed an elastic prosthetic wrap that is designed to apply a gentle mechanical support to the failing heart. The Implant is a compliant elastic structure that is designed to conform to the epicardial surface of the right and left ventricles. It supports the heart throughout the cardiac cycle and was designed to offload the ventricles and reduce wall stress. The objective of this clinical trial is to evaluate the safety and efficacy of the HeartNet Ventricular Support System with optimal medical and device therapy (Treatment group) when compared to optimal medical and device therapy (i.e., medications, cardiac resynchronisation therapy, pacemaker) alone (Control group) as treatments for patients with heart failure. Efficacy of the HeartNet Ventricular Support System in the Treatment group compared to the optimal medical and device therapy Control group will be evaluated based upon cardiopulmonary tests (Peak VO2), six (6) minute walk distance and quality of life assessment, as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire. Safety of the HeartNet Ventricular Support System in the Treatment group compared to the Control group will be evaluated based on the all-cause mortality rate. Paracor Medical intends to submit data obtained in this clinical trial to support a Pre-Market Approval Application to the United States Food and Drug Administration.

Official Title
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Prospective Evaluation of Elastic Restraint to LESSen the Effects of Heart Failure (PEERLESS-HF) Trial

Conditions
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Heart Failure

Intervention / Treatment
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* Device: HeartNet Ventricular Support System
* Drug: Optimal Medical/Device Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic heart failure at enrollment (American College of Cardiology [ACC]/American Heart Association [AHA] Stage C) due to ischemic or nonischemic dilated cardiomyopathy On stable, evidence-based medical and device therapy for heart failure for 3 months prior to randomization <a> Pharmacological Therapy (as appropriate) <i> angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) for patients with ACE inhibitor intolerance or nitrate/hydralazine at the investigators discretion <ii> beta blockers <iii> diuretics, aldosterone inhibitors <b> Ejection fraction < or = to 35% while maintained on optimal medical therapy <c> Cardiac Resynchronization Therapy (CRT), Cardiac Resynchronization Therapy-Defibrillator (CRT-D) <i> If implanted with a CRT or CRT-D, it must be implanted > or = to 3 months before randomization <ii> If currently eligible or anticipated eligibility with a CRT or CRT-D within 6 months, the patient should not be enrolled in the study Specific Qualifying Characteristics Six (6) minute walk of 150 - 450m Peak VO2 for males: 10.0-20.0 ml/kg/min; Peak VO2 for females: 9.0-18.0 ml/kg/min Left ventricular end diastolic diameter (LVEDD) <85mm and index <40mm/m2 (LVEDD/BSA) Heart failure duration > or = to 6 months Exclusion Criteria: Patient History Heart failure due to a reversible condition Hypertrophic obstructive cardiomyopathy (HOCM) Left ventricular assist device (LVAD), intra-aortic balloon pump (IABP) or intravenous inotropes are required or the patient has end stage heart failure despite maintenance on best medical therapy Myxoma Active infection, sepsis, endocarditis, myocarditis or pericarditis Myocardial infarction, stroke, transient ischemic attack, cardiac or other major surgery, or implantable cardioverter defibrillator (ICD) or pacemaker implantation in the 3 months prior to entry Positive pregnancy test for pre-menopausal female Less than 18 years or > or = to 75 years old Hemoglobin level less than 10 gm/dL or creatinine >2.5 mg/dL Uncontrolled medical conditions that increase surgical risk Co-morbid condition that in the investigator's opinion reduces life expectancy to less than 2 years Surgical or Anatomical Considerations Heart measurement too large or small for Implant sizes Restrictive cardiomyopathy Not a candidate for sternotomy or standard thoracotomy surgical approaches Expected to have adhesions from previous surgical procedures History of constrictive pericarditis Previously placed coronary artery bypass grafts (CABG) or anticipated need for coronary artery bypass grafting Not a candidate for cardiopulmonary bypass Anatomical mitral valve regurgitation of 2+ or greater at the time of enrollment Pulmonary function testing with the following results: Forced expiratory volume (FEV1) <1L or if FEV1 is between 1 and 3L, forced expiratory volume divided by forced vital capacity (FEV1/FVC) <60% Cardiac or thoracic condition that might require operative correction. Cardiac transplantation is not included in this exclusion criterion. Other elective surgical procedure at the time of the index hospitalization or within 30 days, whichever is longer Other Any other medical condition that, in the judgment of the investigator, makes the patient a poor candidate for this procedure Currently enrolled or has participated in the last 30 days in another therapeutic or interventional clinical study Unwilling/unable to comply with follow-up Unwilling/unable to give signed informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>HeartNet and Optimal Medical/Device Therapy (e.g., medications and cardiac resynchronisation therapy) | Device: HeartNet Ventricular Support System<br>* The HeartNet Implant is placed on the epicardial surface of the heart surrounding both the left and right ventricles.<br>* Other names: cardiac support;|
| Active Comparator: Control<br>Optimal Medical/Device Therapy alone (e.g., medications and/or cardiac resynchronisation therapy) (Note: For the purpose of the PEERLESS-HF study, optimal medical therapy is defined as the use of angiotensin converting enzyme (ACE) inhibitors and Beta blockers in the highest tolerable doses for three months prior to study enrollment, and Optimal device therapy is defined as cardiac resynchronization therapy (CRT) or cardiac resynchronization therapy-defibrillator (CRT-D) for at least three months prior to study enrollment, when indicated.) | Drug: Optimal Medical/Device Therapy<br>* Optimal Medical/Device Therapy - For the purpose of the PEERLESS-HF study, optimal medical therapy is defined as the use of ACE inhibitors and Beta blockers in the highest tolerable doses for three months prior to study enrollment, and Optimal device therapy is defined as CRT or CRT-D for at least three months prior to study enrollment, when indicated.<br>* Other names: heart failure medications;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Analysis - Peak Oxygen Uptake (Peak VO2) | A participant was considered a responder if cardiopulmonary exercise testing demonstrated an improvement in peak VO2 of at least 1.0 ml/kg/min at 6 months as compared to baseline. | Baseline to 6 months | 
| Responder Analysis - Six (6) Minute Walk (6MW) Distance | A participant was considered a responder if 6MW distance at 6 months was at least 45 meters more than at baseline. | Baseline to 6 months | 
| Responder Analysis - Minnesota Living With Heart Failure (MLWHF) Quality of Life Overall Score | A participant was considered a responder if the MLHF overall score had improved by at least 7 points at 6 months as compared to baseline. THE MLHF questionnaire evaluates the impact of heart failure (HF) on a subject's physical, emotional, social and mental aspects of quality of life. Each of 21 questions about how much HF impacts daily activities is scored from 0-no impact to 5-very much (overall score can range from 0 to 105). Improvement is indicated by a decrease in score. | baseline to 6 months | 
| Number of Participant Deaths | Total number of participants who died within 12 months of enrollment into the trial. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in New York Heart Association (NYHA) Functional Class | Change in NYHA functional class between baseline and 6 months. Maintained means the participant's functional class remained the same as baseline. Improved means the participant's functional class improved (became lower in number) by at least one class. Worsened means the participant's functional class deteriorated (became higher in number) by at least one class. | baseline to 6 months | 
| Change in Quality of Life as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) | The KCCQ is a 23-item questionnaire that quantifies physical function, symptoms, social function, self-efficacy/knowledge and quality of life. Scores range from 0 to 100, where higher scores reflect better health status. For this outcome measure, the difference between each participant's baseline and 6-month KCCQ scores was calculated. The mean change for each treatment arm is presented. | baseline to 6 months | 
| Change in Left Ventricular Mass | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular mass was calculated. The median change for each treatment arm is presented. A decrease in mass is associated with an improvement in the participant's structural heart failure. | baseline to 6 months | 
| Responder Analysis - Peak Oxygen Uptake (Peak VO2) | A participant was considered a responder if cardiopulmonary exercise testing demonstrated an improvement in peak VO2 of at least 1.0 ml/kg/min at 12 months as compared to baseline. | baseline to 12 months | 
| Responder Analysis - Six (6) Minute Walk (6MW) Distance | A participant was considered a responder if 6MW distance at 12 months was at least 45 meters more than at baseline. | baseline to 12 Months | 
| Responder Analysis - Minnesota Living With Heart Failure (MLWHF) Quality of Life Overall Score | A participant was considered a responder if the MLHF overall score had improved by at least 7 points at 12 months as compared to baseline. THE MLHF questionnaire evaluates the impact of heart failure (HF) on a subject's physical, emotional, social and mental aspects of quality of life. Each of 21 questions about how much HF impacts daily activities is scored from 0-no impact to 5-very much (overall score can range from 0 to 105). Improvement is indicated by a decrease in score. | baseline to 12 months | 
| Heart Failure Hospitalization - Actuarial Analysis | Kaplan-Meier actuarial analysis of heart failure hospitalization (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment | 12 months | 
| Change in Left Ventricular End Diastolic Volume | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular end diastolic volume was calculated. The median change for each treatment arm is presented. A decrease in volume is associated with an improvement in the participant's structural heart failure. | baseline to 6 months | 
| Change in Left Ventricular End Systolic Volume | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular end systolic volume was calculated. The median change for each treatment arm is presented. A decrease in volume indicates an improvement in the participant's structural heart failure. | baseline to 6 months | 
| Change in Ejection Fraction | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular ejection fraction was calculated. The median change for each treatment arm is presented. | baseline to 6 months | 
| Change in Left Ventricular End Diastolic Diameter | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular end diastolic diameter was calculated. The median change for each treatment arm is presented. A decrease in diameter indicates an improvement in the participant's structural heart failure. | baseline to 6 months | 
| Change in Left Ventricular End Systolic Diameter | The difference between each participant's baseline and 6-month echocardiographic measure of left ventricular end systolic diameter was calculated. The median change for each treatment arm is presented. A decrease in diameter indicates an improvement in the participant's structural heart failure. | baseline to 6 months | 
| Technical Success (Number of Treatment Arm Participants Successfully Implanted) | Technical success refers to the ability to successfully deliver a device onto the epicardial surface and leave the device in a satisfactory position. Participants who did not undergo an implant procedure were excluded from this analysis. | 1 day | 
| Heart Failure Death | Number of participants who died within 12 months of enrolling in the study and whose cause of death was classified, by an independent Clinical Events Committee, as heart failure | 12 months | 
| Heart Failure Death - Actuarial Analysis | Kaplan-Meier actuarial time-to-event analysis of deaths classified, by an independent Clinical Events Committee, as due to heart failure | 12 months | 
| Heart Failure Hospitalization | Number of participants who experienced a heart failure hospitaliz (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment. | 12 months | 
| All-Cause Hospitalization | Number of participants who experienced a hospitalization (for any cause) within the first 12 months after enrollment. Within the Treatment Arm, hospitalization for the implant procedure was not included in this analysis. | 12 months | 
| All-Cause Hospitalization - Actuarial Analysis | Kaplan-Meier actuarial time-to-first-event analysis of all-cause hospitalizations | 12 months | 
| Participants Experiencing Serious Adverse Events | Number of participants who experienced a serious adverse event (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment | 12 months | 
| Serious Adverse Events - Actuarial Analysis | Kaplan-Meier actuarial time-to-first-event analysis of serious adverse events | 12 months | 
| Days Alive Out of Hospital | Median number of days participants were not hospitalized within the first 12 months after enrollment. Within the Treatment Arm, hospitalization for the implant procedure was not included in this analysis. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PEERLESS-HF, heart failure, cardiac support, Paracor, HeartNet