Back to results

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure (HARPS)

Primary Purpose

Heart Failure, Dilated Cardiomyopathy

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

clenbuterol

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring heart failure, dilated cardiomyopathy, heart assist device, clenbuterol, adrenergic beta agonists, heart transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Georgetown Hospital
Northwestern University
University of Michigan Health System
Montefiore Medical Center
Ohio State University
University of Pennsylvania
Texas Heart Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LVAD and Clenbuterol

Arm Description

Outcomes

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

Secondary Outcome Measures

The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted

Number of Subjects Who Received Maximum Target Dose of Clenbuterol

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

Time from LVAD placement to explant for the single participant who achieved explant

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

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

Mean Change in EuroQoL Visual Analog Scale (EQ5D-VAS) From Baseline to 6 Months and 1 Year Following Device Implant

Scale 0 - 100 where 0 is worst possible health state and 100 is perfect health.

Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 6 Months

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Mean Change in Left Ventricular Ejection Fraction From Device Implant to Completion of Clenbuterol Therapy

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

Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 1 Year Following Device Implant

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Full Information

NCT ID

NCT00585546

First Posted

December 26, 2007

Last Updated

May 16, 2017

Sponsor

Francis D. Pagani

Collaborators

Georgetown University, Montefiore Medical Center, Northwestern University, Ohio State University, Texas Heart Institute, University of Minnesota, University of Pennsylvania, Thoratec Corporation

1. Study Identification

Unique Protocol Identification Number

NCT00585546

Brief Title

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

Acronym

HARPS

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.

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Terminated

Why Stopped

No longer could obtain clenbuterol

Study Start Date

July 2007 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Francis D. Pagani

Collaborators

Georgetown University, Montefiore Medical Center, Northwestern University, Ohio State University, Texas Heart Institute, University of Minnesota, University of Pennsylvania, Thoratec Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure, Dilated Cardiomyopathy

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LVAD and Clenbuterol

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

clenbuterol

Other Intervention Name(s)

Spiropent

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Secondary Outcome Measure Information:

Title

The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted

Time Frame

Maximum 12 months after LVAD implantation

Title

Number of Subjects Who Received Maximum Target Dose of Clenbuterol

Time Frame

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

Title

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

Description

Time from LVAD placement to explant for the single participant who achieved explant

Time Frame

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

Title

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

Time Frame

18 months after explantation

Title

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

Time Frame

Up to 8 weeks after LVAD implantation

Title

Mean Change in EuroQoL Visual Analog Scale (EQ5D-VAS) From Baseline to 6 Months and 1 Year Following Device Implant

Description

Scale 0 - 100 where 0 is worst possible health state and 100 is perfect health.

Time Frame

1 year following LVAD implantation

Title

Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 6 Months

Description

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Time Frame

6 months following LVAD implantation

Title

Mean Change in Left Ventricular Ejection Fraction From Device Implant to Completion of Clenbuterol Therapy

Time Frame

up to 16 months, variable based on length of time receiveing clenbuterol

Title

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

Time Frame

baseline to week 8 post clenbuterol

Title

Mean Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to 1 Year Following Device Implant

Description

Scale 0 - 105 (0- 5 on 21 items) where 0 means heart failure has not limited daily life at all and high scores mean that daily functions are greatly limited.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leslie W. Miller, MD

Organizational Affiliation

Georgetown University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Keith D. Aaronson, MD, MS

Organizational Affiliation

University of Michigan

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Francis D. Pagani, MD, PhD

Organizational Affiliation

University of Michigan

Official's Role

Study Director

Facility Information:

Facility Name

Georgetown Hospital

City

Washington, D.C.

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Michigan Health System

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Montefiore Medical Center

City

The Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

Ohio State University

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19014

Country

United States

Facility Name

Texas Heart Institute

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17079761

Citation

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.

Results Reference

background

Learn more about this trial

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

We'll reach out to this number within 24 hrs