Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
Condition: Heart Failure; Dilated Cardiomyopathy
MeSH terms: Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated
Intervention: clenbuterol
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.
Intervention MeSH terms: Clenbuterol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: heart failure; dilated cardiomyopathy; heart assist device; clenbuterol; adrenergic beta agonists; heart transplantation

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.
    

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