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Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure (HARPS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by University of Michigan.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Georgetown University
Montefiore Medical Center
Northwestern University
Ohio State University
Texas Heart Institute
University of Minnesota - Clinical and Translational Science Institute
University of Pennsylvania
Thoratec Corporation
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00585546
First received: December 26, 2007
Last updated: October 27, 2008
Last verified: October 2008
History of Changes

December 26, 2007
October 27, 2008
July 2007
July 2012   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00585546 on ClinicalTrials.gov Archive Site
  • The proportion of evaluable subjects meeting explant criteria and subsequently explanted [ Time Frame: Maximum 16 months after LVAD implantation ] [ Designated as safety issue: No ]
  • Safety and tolerability of clenbuterol [ Time Frame: 16 months after LVAD implantation ] [ Designated as safety issue: Yes ]
  • To determine the time course of reverse remodeling on a left ventricular assist device during phase I (heart failure medications) and phase II (clenbuterol) of the HARPS protocol [ Time Frame: Up to 16 months after LVAD implantation ] [ Designated as safety issue: No ]
  • To determine the time course and sustainability of reverse remodeling following LVAD explantation [ Time Frame: 1 year after explantation ] [ Designated as safety issue: No ]
  • To assess the biochemical, structural, cellular and molecular changes in the myocardium resulting from the HARPS protocol interventions [ Time Frame: Up to 28 months following LVAD implantation (up to 16 months after LVAD implantation plus 1 year after explantation) ] [ Designated as safety issue: No ]
  • To determine predictors of recovery of left ventricular function/remodeling and of LVAD removal [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
  • To assess changes in body mass, lean muscle mass, muscle strength and maximal and submaximal exercise capacity [ Time Frame: Up to 22 months following LVAD implantation (up to 16 months following LVAD implantation and 6 months following LVAD explantation) ] [ Designated as safety issue: No ]
  • To assess changes in renal function and hepatic enzymes [ Time Frame: Up to 28 months after LVAD implantation ] [ Designated as safety issue: Yes ]
  • To assess changes in quality of life, as measured by the EuroQoL (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) questionnaires [ Time Frame: Up to 28 months following LVAD implantation ] [ Designated as safety issue: No ]
  • To assess changes in systemic inflammation, circulating progenitor cells and growth factors [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
  • The proportion of evaluable subjects meeting explant criteria and subsequently explanted [ Time Frame: Maximum 16 months after LVAD implantation ] [ Designated as safety issue: No ]
  • Safety and tolerability of clenbuterol [ Time Frame: 16 months after LVAD implantation ] [ Designated as safety issue: Yes ]
  • To determine the time course of reverse remodeling on a left ventricular assist device during phase I (heart failure medications) and phase II (clenbuterol) of the HARPS protocol [ Time Frame: Up to 16 months after LVAD implantation ] [ Designated as safety issue: No ]
  • To determine the time course and sustainability of reverse remodeling remodeling following LVAD explantation [ Time Frame: 1 year after explantation ] [ Designated as safety issue: No ]
  • To assess the biochemical, structural, cellular and molecular changes in the myocardium resulting from the HARPS protocol interventions [ Time Frame: Up to 28 months following LVAD implantation (up to 16 months after LVAD implantation plus 1 year after explantation) ] [ Designated as safety issue: No ]
  • To determine predictors of recovery of left ventricular function/remodeling and of LVAD removal [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
  • To assess changes in body mass, lean muscle mass, muscle strength and maximal and submaximal exercise capacity [ Time Frame: Up to 22 months following LVAD implantation (up to 16 months following LVAD implantation and 6 months following LVAD explantation) ] [ Designated as safety issue: No ]
  • To assess changes in renal function and hepatic enzymes [ Time Frame: Up to 28 months after LVAD implantation ] [ Designated as safety issue: Yes ]
  • To assess changes in quality of life, as measured by the EuroQoL (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) questionnaires [ Time Frame: Up to 28 months following LVAD implantation ] [ Designated as safety issue: No ]
  • To assess changes in systemic inflammation, circulating progenitor cells and growth factors [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

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.

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.
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Heart Failure
  • Dilated Cardiomyopathy
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.
Other Name: Spiropent
Experimental: Intervention
Intervention: Drug: clenbuterol
Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, Banner NR, Khaghani A, Yacoub MH. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
July 2012
July 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
Both
18 Years and older
No
United States
 
NCT00585546
HARPS, (Not applicable)
Yes
Leslie W. Miller, MD, Georgetown University, Washington Hospital Center
University of Michigan
  • Georgetown University
  • Montefiore Medical Center
  • Northwestern University
  • Ohio State University
  • Texas Heart Institute
  • University of Minnesota - Clinical and Translational Science Institute
  • University of Pennsylvania
  • Thoratec Corporation
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
University of Michigan
October 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP