Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

NCT00585546 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: HARPS
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

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.

Conditions

Heart Failure; Dilated Cardiomyopathy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percent of Subjects Who Experience LVAD Removal and Subsequent Freedom From Mechanical Circulatory Support or Heart Transplantation for 1-year After Explantation

  One year after LVAD explant or until transplant or death (if not explanted)

Secondary Outcomes (10)

• The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted

  Maximum 12 months after LVAD implantation

• Number of Subjects Who Received Maximum Target Dose of Clenbuterol

  Up to 16 months after LVAD implantation (12 months after beginning clenbuterol)

• Time to Device Explant for Subjects Meeting Explant Criteria Defined in the Protocol

  Time to explant (but not to be followed for more than 16 months)

• Absolute Change in Left Ventricular Ejection Fraction From Explant to 18 Months Following Device Explant

  18 months after explantation

• Absolute Percent Change in Serum Creatinine and Aspartate Transaminase (AST) From Baseline to Week 8 Post Implant

  Up to 8 weeks after LVAD implantation

Study Arms (1)

LVAD and Clenbuterol

EXPERIMENTAL

Drug: clenbuterol

Interventions

clenbuterol 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.

Also known as: Spiropent

LVAD and Clenbuterol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Francis D. Pagani: lead
• Georgetown University: collaborator
• Montefiore Medical Center: collaborator
• Northwestern University: collaborator
• Ohio State University: collaborator
• Texas Heart Institute: collaborator
• University of Minnesota: collaborator
• University of Pennsylvania: collaborator
• Thoratec Corporation: collaborator

Study Sites (7)

Georgetown Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19014, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 17079761 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Cardiomyopathy, Dilated

Interventions

Clenbuterol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

Because a new standard of care was developed during the start of the trial, the trial was stopped for futility in enrollment. The public should exercise great caution in drawing conclusions from such a small sample size.

Results Point of Contact

• Title: Francis Pagani
• Organization: University of Michigan

fpagani@med.umich.edu

734 647-2894

Study Officials

• Leslie W. Miller, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

• Keith D. Aaronson, MD, MS

  University of Michigan

  STUDY DIRECTOR

• Francis D. Pagani, MD, PhD

  University of Michigan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Cardiac Surgery

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 3, 2008
• Study Start: July 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: December 15, 2017
• Results First Posted: December 15, 2017

Record last verified: 2017-05

Locations

US (7)