Anastrozole in Patients With Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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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).

Official Title
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A Double-blind, Placebo-controlled Phase II Study of Anastrozole in Patients With Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Anastrozole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anastrozole<br>1 mg tablet by mouth once daily for 3 months | Drug: Anastrozole<br>* 1 mg tablet to be taken 1 time daily<br>* Other names: Arimidex;|
| Placebo Comparator: Placebo<br>Placebo tablet by mouth once daily for 3 months | Drug: Placebo<br>* 1 mg tablet to be taken 1 time daily<br>* Other names: Sugar pill manufactured to mimic Anastrozole 1 mg tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Estradiol (E2) Level |  | Baseline, 3 months | 
| Tricuspid Annular Plane Systolic Excursion (TAPSE) |  | Baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six Minute Walk Distance |  | Baseline, 3 months |