Pulmonary Arterial Hypertension
Conditions
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).
Interventions
DRUGPlacebo
1 mg tablet to be taken 1 time daily
DRUGAnastrozole
1 mg tablet to be taken 1 time daily
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma Estradiol (E2) Level | Baseline, 3 months |
| Tricuspid Annular Plane Systolic Excursion (TAPSE) | Baseline, 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Six Minute Walk Distance | Baseline, 3 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anastrozole Anastrozole 1 mg tablet by mouth once daily for 3 months | 12 |
| Placebo Placebo 1 mg tablet by mouth once daily for 3 months | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Anastrozole | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 13 | 60.06 years STANDARD_DEVIATION 11.5 | 59 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 17 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 14 Participants | 6 Participants |
| Region of Enrollment United States | 12 participants | 18 participants | 6 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
| Six minute walk distance | 336 meters STANDARD_DEVIATION 119 | 350 meters STANDARD_DEVIATION 131 | 378 meters STANDARD_DEVIATION 161 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 2 / 6 |
| serious Total, serious adverse events | 2 / 12 | 0 / 6 |
Outcome results
Primary
Plasma Estradiol (E2) Level
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole | Plasma Estradiol (E2) Level | -40 % change from baseline |
| Placebo | Plasma Estradiol (E2) Level | -4 % change from baseline |
Primary
Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole | Tricuspid Annular Plane Systolic Excursion (TAPSE) | 7 % change from baseline |
| Placebo | Tricuspid Annular Plane Systolic Excursion (TAPSE) | 10 % change from baseline |
Secondary
Six Minute Walk Distance
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole | Six Minute Walk Distance | 8 % change from baseline |
| Placebo | Six Minute Walk Distance | -2 % change from baseline |