Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Johns Hopkins University; University of Colorado, Denver; Rhode Island Hospital; Stanford University; Vanderbilt University; Washington University School of Medicine
• Information provided by (Responsible Party): University of Pennsylvania

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

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Study Type :	Interventional (Clinical Trial)
Estimated 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 :	October 2, 2017
Estimated Primary Completion Date :	September 2021
Estimated Study Completion Date :	September 2021

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 Name: 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 :

1. Difference in changes in distance walked in six minutes between anastrozole and placebo groups [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Difference in changes in distance walked in six minutes between anastrozole and placebo groups [ Time Frame: 3 months, 12 months ]
2. Difference in right ventricular function between anastrozole and placebo groups [ Time Frame: 6 months, 12 months ]
3. Difference in changes in plasma NT-proBNP level between anastrozole and placebo groups [ Time Frame: 3 months, 6months,12 months ]
4. Difference in changes in biomarkers between anastrozole and placebo groups [ Time Frame: 3 months, 6months,12 months ]
5. Difference in changes in SF36 between anastrozole and placebo groups [ Time Frame: 3 months, 6months,12 months ]
6. Difference in changes in emPHasis-10 between anastrozole and placebo groups [ Time Frame: 3 months, 6months,12 months ]
7. Difference in changes in actigraphy-measured physical activity between anastrozole and placebo groups [ Time Frame: 3 months, 6months,12 months ]
8. Difference in time-to-clinical worsening (TTCW) between anastrozole and placebo groups [ Time Frame: 12 months ]
9. Difference in changes in bone mineral density between anastrozole and placebo groups [ Time Frame: 12 months ]
10. Difference in side effects between anastrozole and placebo groups at twelve months [ Time Frame: 12 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Contacts

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Contact: Diane Pinder	215-294-9757	pinder@pennmedicine.upenn.edu

Locations

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United States, California
Stanford University	Recruiting
Stanford, California, United States, 94305
Contact: Patricia Del Rosario, RN 650-721-2408 pdelrosa@stanford.edu
Principal Investigator: Roham Zamanian, MD
United States, Colorado
University of Colorado - Denver	Recruiting
Aurora, Colorado, United States, 80045
Contact: Cheri Abott, RN, CCRP Cheryl.Abbott@ucdenver.edu
Principal Investigator: Todd Bull, MD
United States, Maryland
Johns Hopkins University	Recruiting
Baltimore, Maryland, United States, 21218
Contact: Haley Rue hrue1@jhmi.edu
Principal Investigator: Stephen Mathai, MD
United States, Missouri
Washington University	Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Sharon Heuerman, RN 314-747-8174 sheuerman@wustl.edu
Principal Investigator: Murali Chakinala, MD
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kate Boyle 215-294-9755 Kathleen.Boyle@uphs.upenn.edu
Contact: Diane Pinder 215-294-9757 pinder@pennmedicine.upenn.edu
Principal Investigator: Steven Kawut, MD
United States, Rhode Island
Rhode Island Hospital	Recruiting
East Providence, Rhode Island, United States, 02914
Contact: Meghan Ahearn 401-444-2733 Meghan.Ahearn@Lifespan.org
Contact: Heather Morreo HMorreo@Lifespan.org
Principal Investigator: Corey Ventetuolo, MD
United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Shannon Cordell, RN 615-343-8277 shannon.eason@Vanderbilt.Edu
Principal Investigator: Anna Hemnes, MD

Sponsors and Collaborators

University of Pennsylvania

National Heart, Lung, and Blood Institute (NHLBI)

Johns Hopkins University

University of Colorado, Denver

Rhode Island Hospital

Stanford University

Vanderbilt University

Washington University School of Medicine

Investigators

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Principal Investigator:	Steven M Kawut, MD	University of Pennsylvania

More Information

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Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT03229499 History of Changes
Other Study ID Numbers:	827486; R01HL134905 ( U.S. NIH Grant/Contract )
First Posted:	July 25, 2017
Last Update Posted:	January 4, 2019
Last Verified:	October 2018

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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

Keywords provided by University of Pennsylvania:

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

Additional relevant MeSH terms:

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Hypertension; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Anastrozole; Antineoplastic Agents, Hormonal	Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs