Pulmonary Hypertension and Anastrozole Trial (PHANTOM)

University of Pennsylvania

Status and phase: Completed; Phase 2

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Placebo Oral Tablet; Drug: Anastrozole

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03229499

827486

R01HL134905 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups, including a placebo group

Anastrozole

Experimental group

Description:

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

Treatment:

Drug: Anastrozole

Placebo

Placebo Comparator group

Description:

1 tablet taken by mouth once a day for one year

Treatment:

Drug: Placebo Oral Tablet