Pulmonary Hypertension and Anastrozole Trial

NCT ID: NCT03229499

Last Updated: 2024-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2022-07-22

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).

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Anastrozole

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

Group Type: EXPERIMENTAL

Anastrozole

Intervention Type: DRUG

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

1 tablet taken by mouth once a day for one year

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

matching placebo tablet

Interventions

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.

Intervention Type: DRUG

Placebo Oral Tablet

matching placebo tablet

Intervention Type: DRUG

Other Intervention Names

Arimidex

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Rhode Island Hospital

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven M Kawut, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Stanford University

Stanford, California, United States

University of Colorado - Denver

Aurora, Colorado, United States

Johns Hopkins University

Baltimore, Maryland, United States

Washington University

St Louis, Missouri, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

East Providence, Rhode Island, United States

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

Kawut SM, Feng R, Ellenberg SS, Zamanian R, Bull T, Chakinala M, Mathai SC, Hemnes A, Lin G, Doyle M, Andrew R, MacLean M, Stasinopoulos I, Austin E, DeMichele A, Shou H, Minhas J, Song N, Moutchia J, Ventetuolo CE. Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med. 2024 Nov 1;210(9):1143-1151. doi: 10.1164/rccm.202402-0371OC.

Reference Type: DERIVED

PMID: 38747680 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01HL134905

Identifier Type: NIH

Identifier Source: secondary_id

View Link

827486

Identifier Type: -

Identifier Source: org_study_id