Brief Title
Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
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.
Brief 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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Percent of Subjects Who Experience LVAD Removal and Subsequent Freedom From Mechanical Circulatory Support or Heart Transplantation for 1-year After Explantation
Secondary Outcome
The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted
Condition
Heart Failure
Intervention
clenbuterol
Study Arms / Comparison Groups
LVAD and Clenbuterol
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
18
Start Date
July 2007
Completion Date
March 2010
Primary Completion Date
March 2010
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Leslie W. Miller, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00585546
Organization ID
HARPS
Responsible Party
Sponsor-Investigator
Study Sponsor
Francis D. Pagani
Collaborators
Georgetown University
Study Sponsor
Leslie W. Miller, MD, Principal Investigator, Georgetown University
Verification Date
May 2017