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

Phase 3TerminatedNCT00382863

Paracor Medical, Inc220 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

220

Conditions

Heart Failure

Interventions

HeartNet Ventricular Support SystemDEVICE

The HeartNet Implant is placed on the epicardial surface of the heart surrounding both the left and right ventricles.

Optimal Medical/Device TherapyDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Symptomatic heart failure at enrollment (American College of Cardiology \[ACC\]/American Heart Association \[AHA\] Stage C) due to ischemic or nonischemic dilated cardiomyopathy 2. 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 1. Six (6) minute walk of 150 - 450m 2. Peak VO2 for males: 10.0-20.0 ml/kg/min; Peak VO2 for females: 9.0-18.0 ml/kg/min 3. Left ventricular end diastolic diameter (LVEDD) \<85mm and index \<40mm/m2 (LVEDD/BSA) 4. Heart failure duration \> or = to 6 months Exclusion Criteria: Patient History 1. Heart failure due to a reversible condition 2. Hypertrophic obstructive cardiomyopathy (HOCM) 3. 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 4. Myxoma 5. Active infection, sepsis, endocarditis, myocarditis or pericarditis 6. 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 7. Positive pregnancy test for pre-menopausal female 8. Less than 18 years or \> or = to 75 years old 9. Hemoglobin level less than 10 gm/dL or creatinine \>2.5 mg/dL 10. Uncontrolled medical conditions that increase surgical risk 11. Co-morbid condition that in the investigator's opinion reduces life expectancy to less than 2 years Surgical or Anatomical Considerations 1. Heart measurement too large or small for Implant sizes 2. Restrictive cardiomyopathy 3. Not a candidate for sternotomy or standard thoracotomy surgical approaches 4. Expected to have adhesions from previous surgical procedures 5. History of constrictive pericarditis 6. Previously placed coronary artery bypass grafts (CABG) or anticipated need for coronary artery bypass grafting 7. Not a candidate for cardiopulmonary bypass 8. Anatomical mitral valve regurgitation of 2+ or greater at the time of enrollment 9. 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% 10. Cardiac or thoracic condition that might require operative correction. Cardiac transplantation is not included in this exclusion criterion. 11. Other elective surgical procedure at the time of the index hospitalization or within 30 days, whichever is longer Other 1. Any other medical condition that, in the judgment of the investigator, makes the patient a poor candidate for this procedure 2. Currently enrolled or has participated in the last 30 days in another therapeutic or interventional clinical study 3. Unwilling/unable to comply with follow-up 4. Unwilling/unable to give signed informed consent

Locations (35)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: baseline to 6 months

Number of Participant Deaths

Total number of participants who died within 12 months of enrollment into the trial.

Time frame: 12 months

Secondary Outcomes

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.

Time frame: baseline to 6 months

Data from ClinicalTrials.gov

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University of Alabama Birmingham

Birmingham, Alabama, United States

USC Keck School of Medicine

Los Angeles, California, United States

University of California, San Francisco, Medical Center

San Francisco, California, United States

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Christiana Care Health System

Newark, Delaware, United States

University of Florida

Gainesville, Florida, United States

Emory University

Atlanta, Georgia, United States

Midwest Heart Foundation

Lombard, Illinois, United States

St. Vincent Hospital and Health Services

Indianapolis, Indiana, United States

Genesis Medical Center

Davenport, Iowa, United States

...and 25 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 12 months

All-Cause Hospitalization - Actuarial Analysis

Kaplan-Meier actuarial time-to-first-event analysis of all-cause hospitalizations

Time frame: 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

Time frame: 12 months

Serious Adverse Events - Actuarial Analysis

Kaplan-Meier actuarial time-to-first-event analysis of serious adverse events

Time frame: 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.

Time frame: 12 months