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
  Purpose

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.


Condition Intervention
Heart Failure
Dilated Cardiomyopathy
Drug: clenbuterol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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.

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
Study Start Date: July 2007
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00585546

Locations
United States, District of Columbia
Georgetown Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Leslie C. Sweet, RN    202-877-7602    Leslie.C.Sweet@medstar.net   
Principal Investigator: Leslie W. Miller, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Charity Ball, RN    312-926-5517    c-ball@northwestern.edu   
Principal Investigator: John O'Connell, MD         
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Christina L. Leventhal, MS    734-647-7958    harps_study@umich.edu   
Sub-Investigator: Keith D. Aaronson, MD, MS         
Principal Investigator: Francis D. Pagani, MD, PhD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Audrey Kleet    718-920-2747    AKLEET@montefiore.org   
Contact: Evonne Fung    718-920-8576    efung@montefiore.org   
Principal Investigator: Simon Maybaum, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Laura Yamokoski    614-247-7793    Laura.Yamokoski@osumc.edu   
Contact: Leah Sanuk    614-292-6789    Leah.Sanuk@osumc.edu   
Principal Investigator: David Feldman, MD, PhD         
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19014
Contact: Kim Craig    215-662-6900    craigk@uphs.upenn.edu   
Principal Investigator: Mariell Jessup, MD         
Sub-Investigator: Rohinton Morris, MD         
United States, Texas
Texas Heart Institute Recruiting
Houston, Texas, United States, 77030
Contact: Kathy Vershave    832-355-8520    kvershave@heart.thi.tmc.edu   
Principal Investigator: Roberta Bogaev, MD         
Sponsors and Collaborators
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
Investigators
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
  More Information

Publications:
Responsible Party: Leslie W. Miller, MD, Georgetown University, Washington Hospital Center
ClinicalTrials.gov Identifier: NCT00585546     History of Changes
Obsolete Identifiers: NCT00701116
Other Study ID Numbers: HARPS, (Not applicable)
Study First Received: December 26, 2007
Last Updated: October 27, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
heart failure
dilated cardiomyopathy
heart assist device
clenbuterol
adrenergic beta agonists
heart transplantation

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Heart Failure
Cardiomyopathies
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Adrenergic Agents
Clenbuterol
Adrenergic beta-Agonists
Adrenergic Agonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Sympathomimetics

ClinicalTrials.gov processed this record on August 27, 2014