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

Primary Purpose

Pulmonary Arterial Hypertension

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fulvestrant

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Fulvestrant

Arm Description

500 mg administered intramuscularly (as two 5 mL injections) on days 0, 14, 28 and 56

Outcomes

Primary Outcome Measures

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

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

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02911844

First Posted

September 19, 2016

Last Updated

December 6, 2019

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT02911844

Brief Title

Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

Acronym

ERA-PAH

Official Title

Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

April 10, 2017 (Actual)

Primary Completion Date

December 5, 2018 (Actual)

Study Completion Date

December 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fulvestrant

Arm Type

Other

Arm Description

500 mg administered intramuscularly (as two 5 mL injections) on days 0, 14, 28 and 56

Intervention Type

Drug

Intervention Name(s)

Fulvestrant

Other Intervention Name(s)

Faslodex

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change From Baseline of Plasma Estradiol Levels

Description

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

Time Frame

Baseline to 9 weeks

Title

Change From Baseline of Tricuspid Annular Plane Systolic Excursion (TAPSE)

Description

Measure obtained from echocardiogram completed on participants Difference in change from baseline to 9 weeks in TAPSE

Time Frame

Baseline to 9 weeks

Title

Change From Baseline of Six Minute Walk Distance

Description

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

Time Frame

Baseline to 9 weeks

Title

Change From Baseline of Plasma NT-proBNP Level

Description

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

Time Frame

Baseline to 9 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven M Kawut, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31314997

Citation

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.

Results Reference

result

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Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

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