Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
- Registration Number
- NCT00585546
- Lead Sponsor
- Francis D. Pagani
- Brief Summary
The purpose of this study is to evaluate whether patients with chronic heart failure not due to coronary artery disease who require use of a left ventricular assist device (LVAD) for refractory heart failure can recover sufficient heart function to allow the pump to be explanted. The study aims to avoid the need for transplantation in these patients by using standard heart failure medications to reduce the size of the left ventricle and then using the investigational drug, clenbuterol, to further improve left ventricular function.
- Detailed Description
The hypothesis of this study is that patients with dilated nonischemic cardiomyopathy who require support with an implanted left ventricular assist device (LVAD) for chronic refractory heart failure can, with a specific two-staged medical regimen designed to enhance maximal reverse remodeling (an angiotensin converting enzyme inhibitor, beta blocker, angiotensin receptor blocker, aldosterone antagonist and digoxin \[stage 1\]) and prevent/reverse myocardial atrophy (the β2 agonist clenbuterol \[stage 2\]), recover adequate left ventricular systolic function to allow LVAD explantation and subsequent intermediate-term survival without need for mechanical circulatory support or heart transplantation.
Within one year of this study's start, a new LVAD became the standard of care for implantation, so the study device became an inferior standard of care shortly thereafter. By 2012 the trial was stopped for futility in enrollment. Thus, certain original outcomes have been deleted, specifically because there was only a single subject explanted, multivariate analysis for sustainability of reverse remodeling following LVAD explantation and predictors of recovery of left ventricular function/remodeling and of LVAD removal could not be done.
Similarly, and for lack of funding, biobank components were not collected; therefore no data exists to present biochemical, structural, cellular and molecular changes in the myocardium resulting from the HARPS protocol interventions, changes in systemic inflammation, circulating progenitor cells and growth factors, or DEXA scan based data: changes in body mass, lean muscle mass, muscle strength and maximal and submaximal exercise capacity. All remaining outcome measures have been edited to more precisely show the outcome measures intended.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
Patients with refractory symptomatic heart failure (NYHA Class IV, or Stage D) due to dilated, non-ischemic cardiomyopathy who meet the following criteria:
- Severe clinical heart failure with associated haemodynamic compromise resistant to intensive medical therapy and requiring LVAD implantation
- Duration of heart failure symptoms to be ≥ 12 months prior to LVAD implant
- Documentation of LVEF ≤ 40% at least 1 year prior to LVAD implantation
- LVEF ≤ 30% and cardiomegaly at the time of LVAD implantation as documented by radionuclide or contrast ventriculography or by echocardiography
- Nonischemic etiology confirmed by coronary angiography within two years of enrollment
- Listed for heart transplantation or plan to list for heart transplantation pending successful LVAD implantation in one of the participating centers, as per usual transplant listing policy at each participating center
- >= 18 years of age
- Body surface area >= 1.5 m2
- Have an implantable defibrillator in place or a commitment to implant an ICD prior to hospital discharge
- Have undergone insertion within prior 2 weeks or will be inserted with a Heartmate XVE LVAD with use of antimicrobial prophylaxis and drive line restraining belt
- Not a heart transplant candidate
- Evidence of active acute myocarditis
- Pulmonary Vascular Resistance > 6 Wood Units
- History of previous CVA resulting in significant fixed motor deficit limiting ability to perform exercise testing
- Previous prosthetic replacement of aortic and/or mitral valve(s)
- Hypertrophic obstructive cardiomyopathy
- LVIDD < 5 cm by surface echocardiogram (restrictive cardiomyopathy)
- Irreversible multi-organ failure
- Underlying bleeding disorder, or platelet count < 75,000, INR > 2.5 (without Coumadin), or Hgb < 8.0.
- Pregnant or lactating women or unwilling to utilize two reliable methods of birth control for women of childbearing age
- Receipt of other investigational drug therapy during LVAD support
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LVAD and Clenbuterol clenbuterol -
- Primary Outcome Measures
Name Time Method Percent of Subjects Who Experience LVAD Removal and Subsequent Freedom From Mechanical Circulatory Support or Heart Transplantation for 1-year After Explantation One year after LVAD explant or until transplant or death (if not explanted)
- Secondary Outcome Measures
Name Time Method Time to Device Explant for Subjects Meeting Explant Criteria Defined in the Protocol Time to explant (but not to be followed for more than 16 months) Time from LVAD placement to explant for the single participant who achieved explant
The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted Maximum 12 months after LVAD implantation Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Clenbuterol baseline to week 8 post clenbuterol Number of Subjects Who Received Maximum Target Dose of Clenbuterol Up to 16 months after LVAD implantation (12 months after beginning clenbuterol) Mean Change in Left Ventricular Ejection Fraction From Device Implant to Completion of Clenbuterol Therapy up to 16 months, variable based on length of time receiveing clenbuterol Absolute Change in Left Ventricular Ejection Fraction From Explant to 18 Months Following Device Explant 18 months after explantation Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Implant Up to 8 weeks after LVAD implantation Mean Change in EuroQoL Visual Analog Scale (EQ5D-VAS) From Baseline to 6 Months and 1 Year Following Device Implant 1 year following LVAD implantation Scale 0 - 100 where 0 is worst possible health state and 100 is perfect health.
Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 6 Months 6 months following LVAD implantation Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.
Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 1 Year Following Device Implant 1 year Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.
Trial Locations
- Locations (7)
Northwestern University
🇺🇸Chicago, Illinois, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Texas Heart Institute
🇺🇸Houston, Texas, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Georgetown Hospital
🇺🇸Washington, D.C., District of Columbia, United States
Montefiore Medical Center
🇺🇸The Bronx, New York, United States