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

Phase 2

Terminated

Conditions: Heart Failure

Interventions: Device: HeartNet Ventricular Support System
Drug: Optimal Medical/Device Therapy

Registration Number: NCT00382863

Lead Sponsor: Paracor Medical, Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 220

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	HeartNet Ventricular Support System	HeartNet and Optimal Medical/Device Therapy (e.g., medications and cardiac resynchronisation therapy)
Control	Optimal Medical/Device Therapy	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.)

Primary Outcome Measures

Name	Time	Method
Responder Analysis - Peak Oxygen Uptake (Peak VO2)	Baseline to 6 months	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.
Responder Analysis - Six (6) Minute Walk (6MW) Distance	Baseline to 6 months	A participant was considered a "responder" if 6MW distance at 6 months was at least 45 meters more than at baseline.
Responder Analysis - Minnesota Living With Heart Failure (MLWHF) Quality of Life Overall Score	baseline to 6 months	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.
Number of Participant Deaths	12 months	Total number of participants who died within 12 months of enrollment into the trial.

Secondary Outcome Measures

Name	Time	Method
Change in New York Heart Association (NYHA) Functional Class	baseline to 6 months	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.
Change in Quality of Life as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)	baseline to 6 months	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.
Change in Left Ventricular Mass	baseline to 6 months	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.
Responder Analysis - Peak Oxygen Uptake (Peak VO2)	baseline to 12 months	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.
Responder Analysis - Six (6) Minute Walk (6MW) Distance	baseline to 12 Months	A participant was considered a "responder" if 6MW distance at 12 months was at least 45 meters more than at baseline.
Responder Analysis - Minnesota Living With Heart Failure (MLWHF) Quality of Life Overall Score	baseline to 12 months	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.
Heart Failure Hospitalization - Actuarial Analysis	12 months	Kaplan-Meier actuarial analysis of heart failure hospitalization (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment
Change in Left Ventricular End Diastolic Volume	baseline to 6 months	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.
Change in Left Ventricular End Systolic Volume	baseline to 6 months	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.
Change in Ejection Fraction	baseline to 6 months	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.
Change in Left Ventricular End Diastolic Diameter	baseline to 6 months	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.
Change in Left Ventricular End Systolic Diameter	baseline to 6 months	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.
Technical Success (Number of Treatment Arm Participants Successfully Implanted)	1 day	"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.
Heart Failure Death	12 months	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
Heart Failure Death - Actuarial Analysis	12 months	Kaplan-Meier actuarial time-to-event analysis of deaths classified, by an independent Clinical Events Committee, as due to heart failure
Heart Failure Hospitalization	12 months	Number of participants who experienced a heart failure hospitaliz (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment.
All-Cause Hospitalization	12 months	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.
All-Cause Hospitalization - Actuarial Analysis	12 months	Kaplan-Meier actuarial time-to-first-event analysis of all-cause hospitalizations
Participants Experiencing Serious Adverse Events	12 months	Number of participants who experienced a serious adverse event (as classified by an independent Clinical Events Committee) within the first 12 months after enrollment
Serious Adverse Events - Actuarial Analysis	12 months	Kaplan-Meier actuarial time-to-first-event analysis of serious adverse events
Days Alive Out of Hospital	12 months	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.

Trial Locations

Locations (35): University of Maryland, Division of Cardiology
🇺🇸
Baltimore, Maryland, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
USC Keck School of Medicine
🇺🇸
Los Angeles, California, United States
University of Colorado Health Sciences Center
🇺🇸
Aurora, Colorado, United States
Midwest Heart Foundation
🇺🇸
Lombard, Illinois, United States
University of California, San Francisco, Medical Center
🇺🇸
San Francisco, California, United States
University of Alabama Birmingham
🇺🇸
Birmingham, Alabama, United States
Christiana Care Health System
🇺🇸
Newark, Delaware, United States
Genesis Medical Center
🇺🇸
Davenport, Iowa, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
St. Vincent Hospital and Health Services
🇺🇸
Indianapolis, Indiana, United States
St. Paul Heart Clinic
🇺🇸
St. Paul, Minnesota, United States
Wayne State University/ Oakwood Hospital
🇺🇸
Detroit, Michigan, United States
Caritas St. Elizabeth's Medical Center
🇺🇸
Boston, Massachusetts, United States
Minneapolis VA Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Mid America Heart Institute
🇺🇸
Kansas City, Missouri, United States
BryanLGH Heart Improvement Program
🇺🇸
Lincoln, Nebraska, United States
Morristown Memorial Hospital
🇺🇸
Morristown, New Jersey, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
The Lindner Clinical Trial Center
🇺🇸
Cincinnati, Ohio, United States
The Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Oklahoma Heart Hospital
🇺🇸
Oklahoma City, Oklahoma, United States
Penn State Milton S. Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
The Stern Cardiovascular Center
🇺🇸
Germantown, Tennessee, United States
University of Calgary
🇨🇦
Calgary, Alberta, Canada
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
Inova Heart & Vascular Institute/ Fairfax Hospital
🇺🇸
Falls Church, Virginia, United States
Tennessee Cardiovascular Research Institute
🇺🇸
Nashville, Tennessee, United States
St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
London Health Sciences Centre
🇨🇦
London, Ontario, Canada
St. Boniface General Hospital
🇨🇦
Winnipeg, Manitoba, Canada
Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada
McGill University Hospital Centre
🇨🇦
Montreal, Quebec, Canada
University of Florida
🇺🇸
Gainesville, Florida, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States