Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension (ERA-PAH)

The main purpose of this clinical trial is to examine the feasibility and effects of fulvestrant in post-menopausal women with pulmonary arterial hypertension (PAH). The study will evaluate how well the drug is tolerated. The study will evaluate changes in circulating hematopoietic progenitor cells, plasma hormone levels, NT-proBNP, and other plasma biomarkers after the administration of fulvestrant. Changes in tricuspid annular plane systolic excursion, stroke volume index, right ventricular fractional area change, and other echo parameters after fulvestrant administration will be evaluated as well as changes in distance walked in six minutes.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

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 pulmonary vascular resistance > 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.
• 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.
• Treatment with estrogen or anti-hormone therapy (tamoxifen, anastrozole, 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 or receptor agonists, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators) within three months of enrollment; the dose must be stable for at least 3 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.
• Hormone therapy.
• Use of warfarin or other anticoagulant (use of aspirin is permitted).
• Platelet count <100,000.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fulvestrant; 500 mg administered intramuscularly (as two 5 mL injections) on days 0, 14, 28 and 56	Drug: Fulvestrant; Fulvestrant 500 mg administered intramuscularly into the buttocks slowly as two 5 mL injections, one in each buttock, on days 0, 14, 28 and 56. Fulvestrant 250 mg (one 5 mL injection) will be used in patients with Child-Pugh Class B liver disease.; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Plasma Estradiol Levels	Plasma estradiol levels are obtained and measured from blood samples collected from each participant. Difference in change from baseline to 9 weeks in plasma estradiol levels	Baseline to 9 weeks
Change From Baseline of Tricuspid Annular Plane Systolic Excursion (TAPSE)	Measure obtained from echocardiogram completed on participants Difference in change from baseline to 9 weeks in TAPSE	Baseline to 9 weeks
Change From Baseline of Six Minute Walk Distance	Measure obtained from six minute walk test completed by participants Difference in change from baseline to 9 weeks in the six minute walk test distance	Baseline to 9 weeks
Change From Baseline of Plasma NT-proBNP Level	Plasma NT-proBNP levels are obtained and measured from blood samples collected from each participant. Difference in change from baseline to 9 weeks in plasma NT-proBNP levels	Baseline to 9 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Steven M Kawut, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Kawut SM, Pinder D, Al-Naamani N, McCormick A, Palevsky HI, Fritz J, Smith KA, Mazurek JA, Doyle MF, MacLean MR, DeMichele A, Mankoff DA. Fulvestrant for the Treatment of Pulmonary Arterial Hypertension. Ann Am Thorac Soc. 2019 Nov;16(11):1456-1459. doi: 10.1513/AnnalsATS.201904-328RL. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): December 5, 2018

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimate): September 22, 2016

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

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; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: 824861

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes