Pulmonary Arterial HypertensionPhase 2ERA-PAHNCT02911844

Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

A Phase 2 study testing Fulvestrant in people with Pulmonary Arterial Hypertension, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: Fulvestrant
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 10 Apr 2017to 5 Dec 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 14Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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
Being tested: Fulvestrant
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FulvestrantDrug
Also called Faslodex
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.

Study groups in NCT02911844
Study group	Role	What they receive
Fulvestrant	Other	500 mg administered intramuscularly (as two 5 mL injections) on days 0, 14, 28 and 56 Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to 9 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Apr 20175 Dec 2018

First posted22 Sep 2016 (estimated)
Study start10 Apr 2017
Primary completion5 Dec 2018
Study completion5 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02911844
Sponsor's protocol ID: 824861
Acronym: ERA-PAH
Status last verified: Dec 2019
First submitted: 19 Sep 2016
Last updated: 9 Dec 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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.
PubMed 31314997

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension
ClinicalTrials.gov ID: NCT02911844
Acronym / sponsor ID: ERA-PAH / 824861
Conditions: Pulmonary Arterial Hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Study start: 10 Apr 2017 (actual)
Primary completion: 5 Dec 2018 (actual)
Study completion: 5 Dec 2018 (actual)
First posted: 22 Sep 2016 (estimated)
Results: Posted 9 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Fulvestrant	Other	Drug: Fulvestrant500 mg administered intramuscularly (as two 5 mL injections) on days 0, 14, 28 and 56

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FulvestrantAlso: FaslodexFulvestrant 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.	Drug	Fulvestrant

Primary outcome

Change From Baseline of Plasma Estradiol Levels
Time frame: Baseline to 9 weeks
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)
Time frame: Baseline to 9 weeks
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
Time frame: Baseline to 9 weeks
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
Time frame: Baseline to 9 weeks
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

Results and safety

Results posted to the registry on 9 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fulvestrant	5	5

Primary outcome: Change From Baseline of Plasma Estradiol Levels

Time frame: Baseline to 9 weeks. Median (Inter-Quartile Range). Unit: pg/ml

Measure	Fulvestrant n = 5
Value	-1.26 (-1.7 to -0.26)

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

Time frame: Baseline to 9 weeks. Median (Inter-Quartile Range). Unit: millimeter

Measure	Fulvestrant n = 5
Value	2 (-3 to 5.5)

Primary outcome: Change From Baseline of Six Minute Walk Distance

Time frame: Baseline to 9 weeks. Median (Inter-Quartile Range). Unit: meters

Measure	Fulvestrant n = 5
Value	31 (10 to 32)

Primary outcome: Change From Baseline of Plasma NT-proBNP Level

Time frame: Baseline to 9 weeks. Median (Inter-Quartile Range). Unit: pg/ml

Measure	Fulvestrant n = 5
Value	42.1 (6.7 to 114)

Adverse events

Time frame: 12 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fulvestrant	0 of 5 (0%)	5 of 5 (100%)	0 of 5

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31314997Kawut 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.

Related trials for Pulmonary Arterial Hypertension

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Steven M Kawut, MD principal investigator

University of Pennsylvania

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant in people with Pulmonary Arterial Hypertension, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline of Plasma Estradiol Levels (time frame: Baseline to 9 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02911844, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.