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

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Device: HeartNet Ventricular Support System; Drug: Optimal Medical/Device Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Hospital Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • California
    • Los Angeles, California, United States, 90033
      • USC Keck School of Medicine
    • San Francisco, California, United States, 94143
      • University of California, San Francisco, Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health Sciences Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Lombard, Illinois, United States, 60148
      • Midwest Heart Foundation
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Hospital and Health Services
  • Iowa
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Division of Cardiology
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Caritas St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/ Oakwood Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Medical Center
    • St. Paul, Minnesota, United States, 55102
      • St. Paul Heart Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Mid America Heart Institute
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • BryanLGH Heart Improvement Program
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Stern Cardiovascular Center
    • Nashville, Tennessee, United States, 37205
      • Tennessee Cardiovascular Research Institute
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart & Vascular Institute/ Fairfax Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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) 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 Ejection fraction < or = to 35% while maintained on optimal medical therapy <c> Cardiac Resynchronization Therapy (CRT), Cardiac Resynchronization Therapy-Defibrillator (CRT-D) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; HeartNet and Optimal Medical/Device Therapy (e.g., medications and cardiac resynchronisation therapy)	Device: HeartNet Ventricular Support System; The HeartNet Implant is placed on the epicardial surface of the heart surrounding both the left and right ventricles.; Other Names: cardiac support
Active Comparator: Control; 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; 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.; Other Names: heart failure medications

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Paracor Medical, Inc
• Investigators: Principal Investigator: William T. Abraham, MD, Chief, Division of Cardiovascular Medicine, The Ohio State University

Publications and helpful links

General Publications

• Abraham WT, Anand I, Aranda JM Jr, Boehmer J, Costanzo MR, DeMarco T, Holcomb R, Ivanhoe R, Kolber M, Rayburn B. Randomized controlled trial of ventricular elastic support therapy in the treatment of symptomatic heart failure: rationale and design. Am Heart J. 2012 Nov;164(5):638-45. doi: 10.1016/j.ahj.2012.07.015. Epub 2012 Oct 2.
• Keteyian SJ, Brawner CA, Ehrman JK, Ivanhoe R, Boehmer JP, Abraham WT; PEERLESS-HF Trial Investigators. Reproducibility of peak oxygen uptake and other cardiopulmonary exercise parameters: implications for clinical trials and clinical practice. Chest. 2010 Oct;138(4):950-5. doi: 10.1378/chest.09-2624. Epub 2010 Jun 3.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: September 28, 2006
• First Submitted That Met QC Criteria: September 28, 2006
• First Posted (Estimate): October 2, 2006

Study Record Updates

• Last Update Posted (Estimate): July 13, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: heart failure; cardiac support; Paracor; HeartNet; PEERLESS-HF
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 200