Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

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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