Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

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).

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Anastrozole; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado - Denver
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Six-minute Walk Distance	Change in the distance walked in six minutes adjusted for baseline value and sex	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in Plasma NT-proBNP	Change in log10 NT-proBNP 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.	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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Johns Hopkins University; University of Colorado, Denver; Washington University School of Medicine; National Heart, Lung, and Blood Institute (NHLBI); Vanderbilt University; Stanford University; Rhode Island Hospital
• Investigators: Principal Investigator: Steven M Kawut, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2017
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): July 22, 2022

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: clinical trial; Randomized Controlled Trial; pulmonary hypertension; anastrozole; PAH; pulmonary arterial hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: 827486; R01HL134905 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes