PHANTOM: Pulmonary Hypertension and Anastrozole Trial

Sponsor

University of Pennsylvania (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03229499

Collaborator

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

Enrollment

Locations

Arms

56.8

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Anastrozole Drug: Placebo Oral Tablet	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

Actual Study Start Date :

Dec 7, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anastrozole 1mg (1 tablet)taken by mouth once a day for one year	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. Other Names: Arimidex
Placebo Comparator: Placebo 1 tablet taken by mouth once a day for one year	Drug: Placebo Oral Tablet matching placebo tablet

Arm

Intervention/Treatment

Experimental: Anastrozole

1mg (1 tablet)taken by mouth once a day for one year

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.

Other Names:

Arimidex

Placebo Comparator: Placebo

1 tablet taken by mouth once a day for one year

Drug: Placebo Oral Tablet

matching placebo tablet

Outcome Measures

Primary Outcome Measures

Difference in changes in distance walked in six minutes between anastrozole and placebo groups [6 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Stanford	California	United States	94305
2	University of Colorado - Denver	Aurora	Colorado	United States	80045
3	Johns Hopkins University	Baltimore	Maryland	United States	21218
4	Washington University	Saint Louis	Missouri	United States	63130
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	Rhode Island Hospital	East Providence	Rhode Island	United States	02914
7	Vanderbilt University	Nashville	Tennessee	United States	37232