Anastrozole in Patients With Pulmonary Arterial Hypertension (AIPH)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Anastrozole
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility 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.
- 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
Sites / Locations
- University of Pennsylvania - Penn Presbyterian
- University of Pennsylvania - Perelman Center
- Brown University - Rhode Island Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Anastrozole
Placebo
Arm Description
1 mg tablet by mouth once daily for 3 months
Placebo tablet by mouth once daily for 3 months
Outcomes
Primary Outcome Measures
Plasma Estradiol (E2) Level
Tricuspid Annular Plane Systolic Excursion (TAPSE)
Secondary Outcome Measures
Six Minute Walk Distance
Full Information
NCT ID
NCT01545336
First Posted
February 29, 2012
Last Updated
September 20, 2016
Sponsor
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT01545336
Brief Title
Anastrozole in Patients With Pulmonary Arterial Hypertension
Acronym
AIPH
Official Title
A Double-blind, Placebo-controlled Phase II Study of Anastrozole in Patients With Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anastrozole
Arm Type
Experimental
Arm Description
1 mg tablet by mouth once daily for 3 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet by mouth once daily for 3 months
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Arimidex
Intervention Description
1 mg tablet to be taken 1 time daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill manufactured to mimic Anastrozole 1 mg tablet
Intervention Description
1 mg tablet to be taken 1 time daily
Primary Outcome Measure Information:
Title
Plasma Estradiol (E2) Level
Time Frame
Baseline, 3 months
Title
Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time Frame
Baseline, 3 months
Secondary Outcome Measure Information:
Title
Six Minute Walk Distance
Time Frame
Baseline, 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven M Kawut, MD, MS
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania - Penn Presbyterian
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pennsylvania - Perelman Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Brown University - Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27602993
Citation
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.
Results Reference
result
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Anastrozole in Patients With Pulmonary Arterial Hypertension
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