Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: Fulvestrant
Intervention description: Fulvestrant 500 mg administered intramuscularly into the buttocks slowly as two 5 mL injections, one in each buttock, on days 0, 14, 28 and 56. Fulvestrant 250 mg (one 5 mL injection) will be used in patients with Child-Pugh Class B liver disease.
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this clinical trial is to examine the feasibility and effects of
      fulvestrant in post-menopausal women with pulmonary arterial hypertension (PAH). The study
      will evaluate how well the drug is tolerated. The study will evaluate changes in circulating
      hematopoietic progenitor cells, plasma hormone levels, NT-proBNP, and other plasma biomarkers
      after the administration of fulvestrant. Changes in tricuspid annular plane systolic
      excursion, stroke volume index, right ventricular fractional area change, and other echo
      parameters after fulvestrant administration will be evaluated as well as changes in distance
      walked in six minutes.
    

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
             pulmonary vascular resistance > 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.

          -  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:

          -  Age < 18.

          -  Treatment with estrogen or anti-hormone therapy (tamoxifen, anastrozole, 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 or receptor agonists, endothelin-1
             receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase
             stimulators) within three months of enrollment; the dose must be stable for at least 3
             months prior to Baseline Visit. PAH therapy which is stopped and then restarted or has
             dose changes which are not related to initiation and uptitration will be allowed
             within 3 months prior to the Baseline Visit.

          -  Hormone therapy.

          -  Use of warfarin or other anticoagulant (use of aspirin is permitted).

          -  Platelet count <100,000.

          -  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.