Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure (HARPS)
The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by University of Michigan.
Recruitment status was Recruiting
Recruitment status was Recruiting
Sponsor:
University of Michigan
Collaborators:
Georgetown University
Montefiore Medical Center
Northwestern University
Ohio State University
Texas Heart Institute
University of Minnesota - Clinical and Translational Science Institute
University of Pennsylvania
Thoratec Corporation
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00585546
First received: December 26, 2007
Last updated: October 27, 2008
Last verified: October 2008
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Heart Failure Dilated Cardiomyopathy |
Drug: clenbuterol |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
Resource links provided by NLM:
Further study details as provided by University of Michigan:
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 [ Time Frame: One year after LVAD explant or until transplant or death (if not explanted) ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- The proportion of evaluable subjects meeting explant criteria and subsequently explanted [ Time Frame: Maximum 16 months after LVAD implantation ] [ Designated as safety issue: No ]
- Safety and tolerability of clenbuterol [ Time Frame: 16 months after LVAD implantation ] [ Designated as safety issue: Yes ]
- To determine the time course of reverse remodeling on a left ventricular assist device during phase I (heart failure medications) and phase II (clenbuterol) of the HARPS protocol [ Time Frame: Up to 16 months after LVAD implantation ] [ Designated as safety issue: No ]
- To determine the time course and sustainability of reverse remodeling following LVAD explantation [ Time Frame: 1 year after explantation ] [ Designated as safety issue: No ]
- To assess the biochemical, structural, cellular and molecular changes in the myocardium resulting from the HARPS protocol interventions [ Time Frame: Up to 28 months following LVAD implantation (up to 16 months after LVAD implantation plus 1 year after explantation) ] [ Designated as safety issue: No ]
- To determine predictors of recovery of left ventricular function/remodeling and of LVAD removal [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
- To assess changes in body mass, lean muscle mass, muscle strength and maximal and submaximal exercise capacity [ Time Frame: Up to 22 months following LVAD implantation (up to 16 months following LVAD implantation and 6 months following LVAD explantation) ] [ Designated as safety issue: No ]
- To assess changes in renal function and hepatic enzymes [ Time Frame: Up to 28 months after LVAD implantation ] [ Designated as safety issue: Yes ]
- To assess changes in quality of life, as measured by the EuroQoL (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) questionnaires [ Time Frame: Up to 28 months following LVAD implantation ] [ Designated as safety issue: No ]
- To assess changes in systemic inflammation, circulating progenitor cells and growth factors [ Time Frame: Up to 16 months following LVAD implantation ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 40 |
| Study Start Date: | July 2007 |
| Estimated Study Completion Date: | July 2012 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Intervention |
Drug: 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.
Other Name: Spiropent
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00585546
Locations
| United States, District of Columbia | |
| Georgetown Hospital | Recruiting |
| Washington, District of Columbia, United States, 20010 | |
| Contact: Leslie C. Sweet, RN 202-877-7602 Leslie.C.Sweet@medstar.net | |
| Principal Investigator: Leslie W. Miller, MD | |
| United States, Illinois | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Charity Ball, RN 312-926-5517 c-ball@northwestern.edu | |
| Principal Investigator: John O'Connell, MD | |
| United States, Michigan | |
| University of Michigan Health System | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Christina L. Leventhal, MS 734-647-7958 harps_study@umich.edu | |
| Sub-Investigator: Keith D. Aaronson, MD, MS | |
| Principal Investigator: Francis D. Pagani, MD, PhD | |
| United States, New York | |
| Montefiore Medical Center | Recruiting |
| Bronx, New York, United States, 10467 | |
| Contact: Audrey Kleet 718-920-2747 AKLEET@montefiore.org | |
| Contact: Evonne Fung 718-920-8576 efung@montefiore.org | |
| Principal Investigator: Simon Maybaum, MD | |
| United States, Ohio | |
| Ohio State University | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Laura Yamokoski 614-247-7793 Laura.Yamokoski@osumc.edu | |
| Contact: Leah Sanuk 614-292-6789 Leah.Sanuk@osumc.edu | |
| Principal Investigator: David Feldman, MD, PhD | |
| United States, Pennsylvania | |
| University of Pennsylvania | Not yet recruiting |
| Philadelphia, Pennsylvania, United States, 19014 | |
| Contact: Kim Craig 215-662-6900 craigk@uphs.upenn.edu | |
| Principal Investigator: Mariell Jessup, MD | |
| Sub-Investigator: Rohinton Morris, MD | |
| United States, Texas | |
| Texas Heart Institute | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Kathy Vershave 832-355-8520 kvershave@heart.thi.tmc.edu | |
| Principal Investigator: Roberta Bogaev, MD | |
Sponsors and Collaborators
University of Michigan
Georgetown University
Montefiore Medical Center
Northwestern University
Ohio State University
Texas Heart Institute
University of Minnesota - Clinical and Translational Science Institute
University of Pennsylvania
Thoratec Corporation
Investigators
| Principal Investigator: | Leslie W. Miller, MD | Georgetown University |
| Study Director: | Keith D. Aaronson, MD, MS | University of Michigan |
| Study Director: | Francis D. Pagani, MD, PhD | University of Michigan |
More Information
Publications:
| Responsible Party: | Leslie W. Miller, MD, Georgetown University, Washington Hospital Center |
| ClinicalTrials.gov Identifier: | NCT00585546 History of Changes |
| Obsolete Identifiers: | NCT00701116 |
| Other Study ID Numbers: | HARPS, (Not applicable) |
| Study First Received: | December 26, 2007 |
| Last Updated: | October 27, 2008 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Michigan:
|
heart failure dilated cardiomyopathy heart assist device |
clenbuterol adrenergic beta agonists heart transplantation |
Additional relevant MeSH terms:
|
Cardiomyopathy, Dilated Heart Failure Cardiomyopathies Cardiomegaly Heart Diseases Cardiovascular Diseases Adrenergic Agents Clenbuterol Adrenergic beta-Agonists Adrenergic Agonists Neurotransmitter Agents |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Anti-Asthmatic Agents Respiratory System Agents Therapeutic Uses Sympathomimetics |
ClinicalTrials.gov processed this record on June 17, 2013