Pulmonary Hypertension and Anastrozole Trial

NCT03229499 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 827486R01HL134905
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 7

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

Keywords

Randomized Controlled Trial; clinical trial; anastrozole; pulmonary hypertension; pulmonary arterial hypertension; PAH

Outcome Measures

Primary Outcomes (1)

• Change in Six-minute Walk Distance

  Change in the distance walked in six minutes adjusted for baseline value and sex

  6 months

Secondary Outcomes (7)

• Change in Right Ventricular Function: Tricuspid Annular Systolic Plane Excursion (TAPSE)

  6 months

• Change in Plasma NT-proBNP

  6months

• 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 emPHasis-10 Score Adjusted for Baseline Value and Sex

  6months

• Change in Actigraphy-measured Physical Activity: Change in 7-day Median Daily Vector Magnitude Count

  6months

Study Arms (2)

Anastrozole

EXPERIMENTAL

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

Drug: Anastrozole

Placebo

PLACEBO COMPARATOR

1 tablet taken by mouth once a day for one year

Drug: Placebo Oral Tablet

Interventions

Anastrozole 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.

Also known as: Arimidex

Anastrozole

Placebo Oral Tablet DRUG

matching placebo tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Johns Hopkins University: collaborator
• University of Colorado, Denver: collaborator
• Rhode Island Hospital: collaborator
• Stanford University: collaborator
• Vanderbilt University: collaborator
• Washington University School of Medicine: collaborator

Study Sites (7)

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado - Denver

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

East Providence, Rhode Island, 02914, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 38747680 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Steven M Kawut, MD, MS
• Organization: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine

kawut@upenn.edu

646-352-1654

Study Officials

• Steven M Kawut, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 25, 2017
• Study Start: December 7, 2017
• Primary Completion: July 22, 2022
• Study Completion: July 22, 2022
• Last Updated: May 1, 2024
• Results First Posted: May 1, 2024

Record last verified: 2024-04

Locations

US (7)