Pulmonary Hypertension and Anastrozole Trial

Study Overview
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Brief Summary
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The primary objectives of this study are to determine whether the study drug, anastrozole may improve six minute walk distance at six months compared to placebo and to assess safety and side effects up to twelve months in pulmonary arterial hypertension (PAH).

Official Title
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Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Anastrozole
* Drug: Placebo Oral Tablet


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 and receiving treatment for PAH. 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 significant 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: Age < 18. Current treatment with estrogen, hormone therapy, or anti-hormone therapy (tamoxifen, fulvestrant, etc.) WHO Class IV functional status. History of invasive 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 most recent echocardiography (within 1 year). Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, riociguat, selexipag) within three months of enrollment; the dose must be stable for at least three 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. Hospitalized or acutely ill. Renal failure (creatinine ≥ 2.0). Hypercalcemia. Severe osteoporosis: T score -2.5 to -3.4 without bone modifying treatment OR T score = - 3.5 or lower Child-Pugh Class C cirrhosis. Current or recent (< 3 months) chronic heavy alcohol consumption. Enrollment in a clinical trial or concurrent use of another investigational drug or device within 30 days of screening visit.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anastrozole<br>1mg (1 tablet)taken by mouth once a day for one year | Drug: Anastrozole<br>* Anastrozole is an aromatase inhibitor indicated for: adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.<br>* Other names: Arimidex;|
| Placebo Comparator: Placebo<br>1 tablet taken by mouth once a day for one year | Drug: Placebo Oral Tablet<br>* matching placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in changes in distance walked in six minutes between anastrozole and placebo groups |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in changes in distance walked in six minutes between anastrozole and placebo groups |  | 3 months, 12 months | 
| Difference in right ventricular function between anastrozole and placebo groups |  | 6 months, 12 months | 
| Difference in changes in plasma NT-proBNP level between anastrozole and placebo groups |  | 3 months, 6months,12 months | 
| Difference in changes in biomarkers between anastrozole and placebo groups |  | 3 months, 6months,12 months | 
| Difference in changes in SF36 between anastrozole and placebo groups |  | 3 months, 6months,12 months | 
| Difference in changes in emPHasis-10 between anastrozole and placebo groups |  | 3 months, 6months,12 months | 
| Difference in changes in actigraphy-measured physical activity between anastrozole and placebo groups |  | 3 months, 6months,12 months | 
| Difference in time-to-clinical worsening (TTCW) between anastrozole and placebo groups |  | 12 months | 
| Difference in changes in bone mineral density between anastrozole and placebo groups |  | 12 months | 
| Difference in side effects between anastrozole and placebo groups at twelve months |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Controlled Trial, clinical trial, anastrozole, pulmonary hypertension, pulmonary arterial hypertension, PAH