Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

NCT02911844 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 824861
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (1)

Fulvestrant

OTHER

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

Drug: Fulvestrant

Interventions

Fulvestrant DRUG

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.

Also known as: Faslodex

Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 31314997 RESULT

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Small size Open-label and uncontrolled design, making it difficult to directly attribute the findings to the study intervention Short duration of the study may have affected the results

Results Point of Contact

• Title: Dr. Steven Kawut
• Organization: University of Pennsylvania

kawut@upenn.edu

215-573-0258

Study Officials

• Steven M Kawut, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: September 22, 2016
• Study Start: April 10, 2017
• Primary Completion: December 5, 2018
• Study Completion: December 5, 2018
• Last Updated: December 9, 2019
• Results First Posted: December 9, 2019

Record last verified: 2019-12

Locations

US (1)