Anastrozole in Patients With Pulmonary Arterial Hypertension

Phase 2

Completed

Brief 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablet by mouth once daily for 3 months
Anastrozole	Anastrozole	1 mg tablet by mouth once daily for 3 months

Primary Outcome Measures

Name	Time	Method
Plasma Estradiol (E2) Level	Baseline, 3 months
Tricuspid Annular Plane Systolic Excursion (TAPSE)	Baseline, 3 months

Secondary Outcome Measures

Name	Time	Method
Six Minute Walk Distance	Baseline, 3 months

Locations (3): University of Pennsylvania - Perelman Center
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pennsylvania - Penn Presbyterian
🇺🇸
Philadelphia, Pennsylvania, United States
Brown University - Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States