Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure - Full Text View

Sponsors and Collaborators:	University of Michigan Georgetown University Montefiore Medical Center Northwestern University Ohio State University Texas Heart Institute University of Minnesota University of Pennsylvania Thoratec Corporation
Information provided by:	University of Michigan
ClinicalTrials.gov Identifier:	NCT00585546

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

MedlinePlus related topics: Cardiomyopathy Heart Failure Heart Transplantation

Drug Information available for: Clenbuterol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study
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.

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
Intervention: Experimental	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.

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

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

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:

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.

Responsible Party:	Georgetown University, Washington Hospital Center ( Leslie W. Miller, MD )
Study ID Numbers:	HARPS, (Not applicable)
Study First Received:	December 26, 2007
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00585546 History of Changes
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

Study placed in the following topic categories:

Heart Failure
Neurotransmitter Agents
Heart Diseases
Adrenergic Agents
Adrenergic beta-Agonists
Dilated Cardiomyopathy
Cardiomyopathy, Dilated

Anti-Asthmatic Agents
Cardiomyopathies
Clenbuterol
Adrenergic Agonists
Peripheral Nervous System Agents
Cardiomegaly
Bronchodilator Agents

Additional relevant MeSH terms:

Respiratory System Agents
Heart Failure
Neurotransmitter Agents
Heart Diseases
Adrenergic beta-Agonists
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Sympathomimetics
Cardiomyopathy, Dilated
Physiological Effects of Drugs
Anti-Asthmatic Agents

Cardiomyopathies
Adrenergic Agonists
Clenbuterol
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Cardiovascular Diseases
Peripheral Nervous System Agents
Bronchodilator Agents
Cardiomegaly

ClinicalTrials.gov processed this record on May 07, 2009