Anastrozole in Patients With Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Anastrozole; Placebo
Intervention description: 1 mg tablet to be taken 1 time daily; 1 mg tablet to be taken 1 time daily
Intervention MeSH terms: Anastrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this clinical trial is to study the safety and efficacy of anastrozole in
      adults diagnosed with pulmonary arterial hypertension (PAH). The study will evaluate how well
      the drug is tolerated. The study will also evaluate if anastrozole effects estradiol (E2)
      hormone levels, a sex hormone, and improves the function of the lower right chamber of the
      heart (right ventricle).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previous documentation of mean pulmonary artery pressure > 25 mm Hg with a pulmonary
             capillary wedge pressure (or left ventricular end-diastolic pressure) < 16 mm Hg and
             PVR > 3 WU at any time before study entry.

          -  Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated
             with connective tissue disease, congenital heart disease, portal hypertension, or HIV
             infection.

          -  Most recent pulmonary function tests with FEV1/FVC >50% AND either a) total lung
             capacity > 70% predicted or b) total lung capacity between 60% and 70% predicted with
             no more than mild interstitial lung disease on computerized tomography scan of the
             chest

          -  Ability to perform six minute walk testing without limitations in musculoskeletal
             function or coordination.

          -  If female, post-menopausal state, defined as:

          -  > 50 years old AND

          -  a) have not menstruated during the preceding 12 months OR

          -  b) have follicle-stimulating hormone (FSH) levels (> 40 IU/L) OR

          -  < 50 years and FSH (> 40 IU/L) OR

          -  having had a bilateral oophorectomy

          -  Informed consent

        Exclusion Criteria:

          -  Treatment with estrogen or anti-hormone therapy (tamoxifen, fulvestrant, etc.)

          -  WHO Class IV functional status

          -  History of breast cancer

          -  Clinically significant untreated sleep apnea

          -  Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency
             or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection
             fraction < 45% on echocardiography

          -  Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists,
             phosphodiesterase-5 inhibitors) within three months of enrollment; the dose must be
             stable for at least 3 months prior to Baseline Visit

          -  Hormone therapy

          -  Hospitalized or acutely ill

          -  Renal failure (creatinine > 2.0)

          -  Child-Pugh Class C cirrhosis

          -  Current or recent (< 6 months) chronic heavy alcohol consumption

          -  Current use of another investigational drug (non-FDA approved) for PAH

          -  Enrollment in a clinical trial within one month of screening

          -  Age < 18