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Heart FailurePhase 1HARPSNCT00585546

Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure

A Phase 1 study testing clenbuterol in people with Heart Failure and Dilated Cardiomyopathy, run by Francis D. Pagani at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure, Dilated Cardiomyopathy
What is being tested?
clenbuterol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
7 sitesUnited States
Study dates
Jul 2007to Mar 2010
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Northwestern University

    Chicago, Illinois, 60611

  • Ohio State University

    Columbus, Ohio, 43210

  • Texas Heart Institute

    Houston, Texas, 77030

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19014

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Georgetown Hospital

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

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.

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.

Read the 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.

Being tested
clenbuterol
Keywords
heart failure, dilated cardiomyopathy, heart assist device, clenbuterol, adrenergic beta agonists, heart transplantation
Medical subject headings
Heart Failure, Cardiomyopathy, Dilated

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • clenbuterolDrug

    Also called Spiropent

    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.

Study groups in NCT00585546
Study groupRoleWhat they receive
LVAD and ClenbuterolExperimentalNot described
Receives: Drug: clenbuterol

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (10)

  1. The Number of Evaluable Subjects Meeting Explant Criteria and Subsequently Explanted

    Measured: Maximum 12 months after LVAD implantation

  2. Number of Subjects Who Received Maximum Target Dose of Clenbuterol

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

  3. 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

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

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

    Measured: 18 months after explantation

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

    Measured: Up to 8 weeks after LVAD implantation

  6. 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.

    Measured: 1 year following LVAD implantation

  7. 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.

    Measured: 6 months following LVAD implantation

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

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

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

    Measured: baseline to week 8 post clenbuterol

  10. 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.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2008 (estimated)
  2. Study startJul 2007
  3. Primary completionMar 2010
  4. Study completionMar 2010

Why it stopped: No longer could obtain clenbuterol

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00585546
Sponsor's protocol ID
HARPS
Acronym
HARPS
Status last verified
May 2017
First submitted
26 Dec 2007
Last updated
15 Dec 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 17079761

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing clenbuterol in people with Heart Failure and Dilated Cardiomyopathy, run by Francis D. Pagani at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00585546, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2017.

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