Anastrozole in Patients With Pulmonary Arterial Hypertension (AIPH)

A Double-blind, Placebo-controlled Phase II Study of Anastrozole in Patients With Pulmonary Arterial Hypertension

The main purpose of this clinical trial is to study the safety and efficacy of anastrozole in adults diagnosed with pulmonary arterial hypertension (PAH). The study will evaluate how well the drug is tolerated. The study will also evaluate if anastrozole effects estradiol (E2) hormone levels, a sex hormone, and improves the function of the lower right chamber of the heart (right ventricle).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Perelman Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Penn Presbyterian
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Brown University - Rhode Island Hospital

Participation Criteria

Eligibility Criteria

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

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.
• 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 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:

• Treatment with estrogen or anti-hormone therapy (tamoxifen, fulvestrant, etc.)
• WHO Class IV functional status
• History of 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 echocardiography
• Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors) within three months of enrollment; the dose must be stable for at least 3 months prior to Baseline Visit
• Hormone therapy
• Hospitalized or acutely ill
• Renal failure (creatinine > 2.0)
• Child-Pugh Class C cirrhosis
• Current or recent (< 6 months) chronic heavy alcohol consumption
• Current use of another investigational drug (non-FDA approved) for PAH
• Enrollment in a clinical trial within one month of screening
• Age < 18

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anastrozole; 1 mg tablet by mouth once daily for 3 months	Drug: Anastrozole; 1 mg tablet to be taken 1 time daily; Other Names: Arimidex
Placebo Comparator: Placebo; Placebo tablet by mouth once daily for 3 months	Drug: Placebo; 1 mg tablet to be taken 1 time daily; Other Names: Sugar pill manufactured to mimic Anastrozole 1 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma Estradiol (E2) Level	Baseline, 3 months
Tricuspid Annular Plane Systolic Excursion (TAPSE)	Baseline, 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Six Minute Walk Distance	Baseline, 3 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Publications and helpful links

General Publications

• Kawut SM, Archer-Chicko CL, DeMichele A, Fritz JS, Klinger JR, Ky B, Palevsky HI, Palmisciano AJ, Patel M, Pinder D, Propert KJ, Smith KA, Stanczyk F, Tracy R, Vaidya A, Whittenhall ME, Ventetuolo CE. Anastrozole in Pulmonary Arterial Hypertension. A Randomized, Double-Blind, Placebo-controlled Trial. Am J Respir Crit Care Med. 2017 Feb 1;195(3):360-368. doi: 10.1164/rccm.201605-1024OC.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 29, 2012
• First Submitted That Met QC Criteria: February 29, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; 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: 815035