Pulmonary Hypertension and Anastrozole Trial

Pulmonary Arterial Hypertension Clinical Trial

— PHANTOM  

Official title:

Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03229499
• Other study ID #: 827486
• Secondary ID: R01HL134905
• Status: Completed
• Phase: Phase 2
• Start date: December 7, 2017
• Est. completion date: July 22, 2022

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: July 22, 2022
• Est. primary completion date: July 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 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.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Anastrozole
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.
• Placebo Oral Tablet
matching placebo tablet

Locations

Country	Name	City	State
United States	University of Colorado - Denver	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Rhode Island Hospital	East Providence	Rhode Island
United States	Vanderbilt University	Nashville	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Stanford University	Stanford	California

Sponsors (8)

Lead Sponsor	Collaborator
University of Pennsylvania	Johns Hopkins University, National Heart, Lung, and Blood Institute (NHLBI), Rhode Island Hospital, Stanford University, University of Colorado, Denver, Vanderbilt University, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Six-minute Walk Distance	Change in the distance walked in six minutes adjusted for baseline value and sex	6 months
Secondary	Change in Right Ventricular Function: Tricuspid Annular Systolic Plane Excursion (TAPSE)	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	6 months
Secondary	Change in Plasma NT-proBNP	Change in log10 NT-proBNP adjusted for baseline value and sex	6months
Secondary	Change in the Medical Outcomes Study Questionnaire Short Form-36 (SF36) Physical Component Summary (PCS) Score 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. SF36 PCS score is a subjective measure of physical health status, with scores ranging from 0 to 100. Higher scores represent better health status.	6months
Secondary	Change in the emPHasis-10 Score Adjusted for Baseline Value and Sex	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.	6months
Secondary	Change in Actigraphy-measured Physical Activity: Change in 7-day Median Daily Vector Magnitude Count	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.	6months
Secondary	Number of Participants With a Clinical Worsening Event Between Anastrozole and Placebo Groups	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.	12 months
Secondary	Change in Bone Mineral Density: Lumbar Spine Between Anastrozole and Placebo Groups	Change in lumbar spine bone mineral density adjusted for baseline value and sex between anastrozole and placebo groups	12 months