NCT00585546

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

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.

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Francis D. Pagani · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Heart Failure
• Dilated Cardiomyopathy

Interventions

Type	Name	Description
DRUG	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.

Timeline

• Start date: 2007-07-01
• Primary completion: 2010-03-01
• Completion: 2010-03-01
• First posted: 2008-01-03
• Last updated: 2017-12-15
• Results posted: 2017-12-15

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study