Pulmonary Hypertension and Anastrozole Trial

Phase 2

Completed

Conditions: Pulmonary Arterial Hypertension

Interventions: Drug: Anastrozole
Drug: Placebo Oral Tablet

Registration Number: NCT03229499

Lead Sponsor: University of Pennsylvania

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 84

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anastrozole	Anastrozole	1mg (1 tablet)taken by mouth once a day for one year
Placebo	Placebo Oral Tablet	1 tablet taken by mouth once a day for one year

Primary Outcome Measures

Name	Time	Method
Change in Six-minute Walk Distance	6 months	Change in the distance walked in six minutes adjusted for baseline value and sex

Secondary Outcome Measures

Name	Time	Method
Change in Right Ventricular Function: Tricuspid Annular Systolic Plane Excursion (TAPSE)	6 months	Change in tricuspid annular systolic plane excursion (TAPSE) adjusted for baseline value and sex. TAPSE is a measure of right ventricular function that is measured via cardiac echography
Change in Plasma NT-proBNP	6months	Change in log10 NT-proBNP adjusted for baseline value and sex
Change in the Medical Outcomes Study Questionnaire Short Form-36 (SF36) Physical Component Summary (PCS) Score Adjusted for Baseline Value and Sex.	6months	Change in the Medical Outcomes Study Questionnaire Short Form-36 (SF36) physical component summary (PCS) score adjusted for baseline value and sex. SF36 PCS score is a subjective measure of physical health status, with scores ranging from 0 to 100. Higher scores represent better health status.
Change in the emPHasis-10 Score Adjusted for Baseline Value and Sex	6months	Change in the emPHasis-10 score adjusted for baseline value and sex. EmPHasis-10 is a pulmonary hypertension-specific measure of quality of life which is scored from 0-50, with higher scores indicating worse quality of life.
Change in Actigraphy-measured Physical Activity: Change in 7-day Median Daily Vector Magnitude Count	6months	Actigraphy-measured vector magnitude count is an estimate of physical activity intensity. The total vector magnitude counts per day was measured over 7 days using an actigraphy device, and the median value over the 7 days was obtained. This outcome measure is the change in the 7-day median value from baseline to follow-up, adjusted for the baseline value, sex, and actigraphy device wear time.
Number of Participants With a Clinical Worsening Event Between Anastrozole and Placebo Groups	12 months	Number of participants with a clinical worsening event. Clinical worsening was defined as the addition of new PAH therapies or dose increases in previously stable PAH therapy for increased symptoms, hospitalization for PAH progression and/or right-sided heart failure, lung transplantation, atrial septostomy, or all-cause death.' Unit of Measure is retained as 'Participants.
Change in Bone Mineral Density: Lumbar Spine Between Anastrozole and Placebo Groups	12 months	Change in lumbar spine bone mineral density adjusted for baseline value and sex between anastrozole and placebo groups

Trial Locations

Locations (7): University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Stanford University
🇺🇸
Stanford, California, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
University of Colorado - Denver
🇺🇸
Aurora, Colorado, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States
Rhode Island Hospital
🇺🇸
East Providence, Rhode Island, United States