Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

NCT ID: NCT00585546

Last Updated: 2017-12-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2010-03-31

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.

Conditions

Heart Failure; Dilated Cardiomyopathy

Keywords

heart failure; dilated cardiomyopathy; heart assist device; clenbuterol; adrenergic beta agonists; heart transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LVAD and Clenbuterol

Group Type: EXPERIMENTAL

clenbuterol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Spiropent

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Georgetown University

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

Texas Heart Institute

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Thoratec Corporation

INDUSTRY

Sponsor Role: collaborator

Francis D. Pagani

OTHER

Sponsor Role: lead

Responsible Party

Francis D. Pagani

Professor of Cardiac Surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Leslie W. Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University

Keith D. Aaronson, MD, MS

Role: STUDY_DIRECTOR

University of Michigan

Francis D. Pagani, MD, PhD

Role: STUDY_DIRECTOR

University of Michigan

Locations

Georgetown Hospital

Washington D.C., District of Columbia, United States

Northwestern University

Chicago, Illinois, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Montefiore Medical Center

The Bronx, New York, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Texas Heart Institute

Houston, Texas, United States

Countries

United States

References

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. doi: 10.1056/NEJMoa053063.

Reference Type: BACKGROUND

PMID: 17079761 (View on PubMed)

Other Identifiers

HARPS

Identifier Type: -

Identifier Source: org_study_id

NCT00701116

Identifier Type: -

Identifier Source: nct_alias