Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure (HARPS)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Harefield Recovery Protocol Study (HARPS): A Nonrandomized, Open Label, Multicenter Evaluation of Potential Recovery of Heart Function in Patients With Refractory Chronic Heart Failure by Treatment With Combination of Left Ventricular Assist Device (LVAD), Drugs to Induce Maximal Reverse Remodeling and the Beta-2 Adrenergic Receptor Agonist Clenbuterol.|
- Percent of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation for 1-year after explantation [ Time Frame: One year after LVAD explant or until transplant or death (if not explanted) ] [ Designated as safety issue: No ]
- The number of evaluable subjects meeting explant criteria and subsequently explanted [ Time Frame: Maximum 16 months after LVAD implantation ] [ Designated as safety issue: No ]
- Number of subjects who received maximum target dose of clenbuterol [ Time Frame: Up to 16 months after LVAD implantation ] [ Designated as safety issue: Yes ]
- Median time to device explant for subjects meeting explant criteria defined in the protocol [ Time Frame: Time to explant (but not to be followed for more than 16 months) ] [ Designated as safety issue: No ]
- Change in left ventricular ejection fraction from explant to one year following device explant [ Time Frame: 1 year after explantation ] [ Designated as safety issue: No ]
- Absolute percent change in serum creatinine and aspartate transaminase (AST) from baseline to week 8 post implant and week 8 post clenbuterol [ Time Frame: Up to 24 weeks after LVAD implantation ] [ Designated as safety issue: Yes ]
- Mean change in EuroQoL visual analog scale (EQ5D-VAS) from baseline to 6 months and 1 year following device implant [ Time Frame: 1 year following LVAD implantation ] [ Designated as safety issue: No ]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 and 1 year following device implant [ Time Frame: 12 months following LVAD implantation ] [ Designated as safety issue: No ]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 left ventricular ejection fraction from device implant to completion of clenbuterol therapy [ Time Frame: up to 16 months, variable based on length of time receiveing clenbuterol ] [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
|Experimental: LVAD and Clenbuterol||
Clenbuterol 20 mcg tablets uptitrated from 20 mcg PO TID to a maximally tolerated dose not to exceed 700 mcg PO TID. Patients will then be switched to the equivalent dose of clenbuterol liquid 59 mcg/ml PO TID. Clenbuterol will be administered for a minimum of 3 months and a maximum of 12 months.
Other Name: Spiropent
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00585546
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467|
|United States, Ohio|
|Ohio State University|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19014|
|United States, Texas|
|Texas Heart Institute|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Leslie W. Miller, MD||Georgetown University|
|Study Director:||Keith D. Aaronson, MD, MS||University of Michigan|
|Study Director:||Francis D. Pagani, MD, PhD||University of Michigan|