Clinical trial NCT03229499: Pulmonary Hypertension and Anastrozole Trial
Official title: Pulmonary Hypertension and Anastrozole Trial (PHANTOM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Randomized Controlled Trial
clinical trial
anastrozole
pulmonary hypertension
pulmonary arterial hypertension
PAH
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Johns Hopkins University
name: University of Colorado, Denver
name: Rhode Island Hospital
name: Stanford University
name: Vanderbilt University
name: Washington University School of Medicine
First posted: 2017-07-25
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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 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.

Primary outcomes:
measure: Change in Six-minute Walk Distance
timeFrame: 6 months
Secondary outcomes:
measure: Change in Right Ventricular Function: Tricuspid Annular Systolic Plane Excursion (TAPSE)
timeFrame: 6 months
measure: Change in Plasma NT-proBNP
timeFrame: 6months
measure: Change in the Medical Outcomes Study Questionnaire Short Form-36 (SF36) Physical Component Summary (PCS) Score Adjusted for Baseline Value and Sex.
timeFrame: 6months
measure: Change in the emPHasis-10 Score Adjusted for Baseline Value and Sex
timeFrame: 6months
measure: Change in Actigraphy-measured Physical Activity: Change in 7-day Median Daily Vector Magnitude Count
timeFrame: 6months
measure: Number of Participants With a Clinical Worsening Event Between Anastrozole and Placebo Groups
timeFrame: 12 months
measure: Change in Bone Mineral Density: Lumbar Spine Between Anastrozole and Placebo Groups
timeFrame: 12 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado - Denver
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: University of Pennsylvania
name: Steven M Kawut, MD
role: PRINCIPAL_INVESTIGATOR
References: