Exercise-induced Pulmonary Arterial HypertensionPhase 4EiPAHNCT01338636

An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH)

A Phase 4 study testing Ambrisentan in people with Exercise-induced Pulmonary Arterial Hypertension, run by Brigham and Women's Hospital 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

The purpose of this study is assess whether ambrisentan can help people with exercise- induced pulmonary arterial hypertension (EIPAH). The investigators also want to find out if ambrisentan is safe to take without causing excessive side effects. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Exercise-induced Pulmonary Arterial Hypertension
What is being tested?: Ambrisentan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Sep 2008to May 2016
Phase: Phase 4
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
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The participant provides written informed consent before the commencement of any study related procedure.
The participant is 18 years of age or older.
If a female participant of child-bearing potential, the participant must agree to use 2 forms of contraceptive therapy, including at least 1 barrier method, throughout the study and follow-up. (Women who are surgically sterile or those post-menopausal for at least 2 years are not considered to be of childbearing potential.)
The participant has findings of either exercise induced PAH on an Advanced Level-3 CPET performed within the last 6-months and is a New York Heart Association (NYHA) Class I or II.
The participant has a left ventricular ejection fraction (LVEF) of 55%, obtained by any appropriate method (i.e., echocardiographic assessment (ECHO), radionuclide imaging, or cardiac catheterization)
The participant is taking a stable concomitant medication regimen for at least 4 weeks prior to enrollment in the study that is not expected to change during the study period and follow-up. Changes in diuretic and/or nitrate therapy as needed during the study period are acceptable.

Who cannot join

The participant has clinically significant psychiatric, addictive, neurologic disease or any other condition that, in the Investigator's opinion, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol.
The participant has evidence of unstable cardiovascular disease including intermittent atrial fibrillation or unstable angina within the 4 weeks prior to Screening.
The participant has diagnosis of exercise induced heart failure with preserved ejection fraction (previously diastolic dysfunction).
The participant has amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
The participant has a history of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention within the last 3 months.
The participant has clinically significant valvular heart disease in the opinion of the Investigator.

Show all 21Show fewer

The participant has a history of cerebrovascular accident or transient ischemic attack within the last 3 months.
Participant has a serum alanine transaminase (ALT) or aspartate transaminase (AST) lab value that is greater than 1.5x upper limit of normal (ULN) prior to Baseline Visit.
Participant has discontinued other endothelial receptor agonist (ERA) treatment (e.g. bosentan) for any adverse event.
The participant has, in the opinion of the Investigator, a dependence on alcohol.
The participant has, in the opinion of the Investigator, a dependence on illicit drugs.
The participant has anemia defined as hemoglobin (Hgb) below 10.0 g/dL.
A participant may qualify for the study following diagnosis and treatment of anemia, if the anemia is due to iron and/or vitamin deficiency.
The participant has exercise tolerance limited by noncardiac causes (e.g., exercise-induced asthma, chronic obstructive pulmonary disease, malignancy, obesity, musculoskeletal disorder).
The participant has uncontrolled systemic hypertension defined as a resting blood pressure of 140/90 mmHg if on no treatment for systemic hypertension or 160/90 mmHg if on 2 systemic hypertension medications. For participants who are receiving treatment for diabetes mellitus, uncontrolled systemic hypertension is defined as ≥ 130/80 mmHg.
The participant has the presence, or history, of malignancy that required significant medical intervention within the preceding 3 months and/or is likely to result in death within the next 2 years.
The participant has chronic renal impairment or renal insufficiency defined by a serum creatinine 2.5 mg/dL and/or the requirement for dialysis.
The participant is lactating, breastfeeding, or pregnant.
The participant received any chronic prostacyclin, prostacyclin analogue, ERA, or phosphodiesterase (PDE) inhibitor therapy within the 30 days prior to study entry. The use of PDE inhibitors "as needed" for erectile dysfunction is acceptable as long as the participant is not dosed within 24 hours of an efficacy assessment.
The participant has a documented allergy to Lidocaine.
Have received any investigational medication within 30 days prior to the start of this study or be scheduled to receive another investigational drug during the course of this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial Hypertension

Read the detailed description

EIPAH population: These participants may provide a unique window into the pathogenesis of PAH. Our data suggest that these participants may represent an early phase of PAH with an abnormal vascular response.

The study includes an assessment of the potential impact of ambrisentan on the exercise capacity Advanced Level-3 cardiopulmonary exercise test (CPET) and the World Health Organization functional class (WHO FC).

Conditions: Exercise-induced Pulmonary Arterial Hypertension
Being tested: Ambrisentan
Keywords: Exercise-induced pulmonary arterial hypertension (EIPAH), Pulmonary arterial hypertension (PAH), ambrisentan, Advanced cardiopulmonary exercise test (CPET)
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.

AmbrisentanDrug
Also called Letairis
5 mg orally every day for 4 weeks. At Week 4, if ambrisentan 5 mg was tolerated, the dose was increased to 10 mg every day for the remainder of the 24-week period.

Study groups in NCT01338636
Study group	Role	What they receive
Exercise-induced PAH	Other	Open-label ambrisentan Receives: Drug: Ambrisentan

What is being measured

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

Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)
mPAP is measure of the blood pressure found in the main artery of the lung. TPG is the difference between mean pulmonary arterial pressure and left atrial pressure. PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.
Measured: Baseline to Week 24
Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)
PVR is the resistance offered by the pulmonary circulatory system.
Measured: Baseline to Week 24
Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )
PVC is a measure of a pulmonary vein's ability to expand.
Measured: Baseline to Week 24
Change From Baseline in Peak Exercise Cardiac Output (CO)
CO is the amount of blood pumped by the heart per minute.
Measured: Baseline to Week 24
Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max)
VO2max is the measurement of the maximum amount of oxygen that an individual can utilize during intense or maximal exercise.
Measured: Baseline to Week 24

Secondary outcomes (3)

Change From Baseline in 6-minute Walk Distance (6MWD)
6MWD is the distance walked by the participant in 6 minutes.
Measured: Baseline to Week 24
Borg Dyspnea Scale Score
The Borg Dyspnea Scale measures how breathless the participant feels. Scores range from 0 (no shortness of breath) to 10 (more short of breath than ever experienced). (minimum score 0, maximum score 10 with 10 being worsening outcome)
Measured: Baseline and Week 24
World Health Organization Functional Class (WHO FC)
The WHO FC categorizes cardiac disability using four classes, ranging from Class 1 (without limitation of physical activity) to Class 4 (inability to carry on any physical activity without discomfort).
Measured: Baseline and Week 24

Timeline

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

Sep 2008May 2016

First posted19 Apr 2011 (estimated)
Study startSep 2008
Primary completionFeb 2016
Study completionMay 2016

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.
Other trials for Exercise-induced Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe 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 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01338636
Sponsor's protocol ID: 2008P000687
Acronym: EiPAH
Status last verified: Jan 2022
First submitted: 18 Apr 2011
Last updated: 18 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
Individual data sharing: No

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

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Rehabilitation Program for People With Methamphetamine-Associated Cardiopulmonary Conditions
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RecruitingEarly Phase 1
Early Intervention With Inhaled Treprostinil Among Patients With Exercise-Induced Pulmonary Hypertension (EPIH)
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Recruiting
Exercise Performance on Ambient Air vs. Low-Flow Liquid Oxygen Therapy in Pulmonary Vascular Disease (PVD)
Pulmonary Vascular Disease, Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Recruiting
Exercise Performance on Ambient Air vs. Low-Flow Liquid Oxygen Therapy in Chronic Lung Diseases
Pulmonary Vascular Disease, Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Recruiting
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All Exercise-induced Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial Hypertension
ClinicalTrials.gov ID: NCT01338636
Acronym / sponsor ID: EiPAH / 2008P000687
Conditions: Exercise-induced Pulmonary Arterial Hypertension
Keywords: Exercise-induced pulmonary arterial hypertension (EIPAH), Pulmonary arterial hypertension (PAH), ambrisentan, Advanced cardiopulmonary exercise test (CPET)
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: Gilead Sciences
Study start: Sep 2008
Primary completion: Feb 2016 (actual)
Study completion: May 2016 (actual)
First posted: 19 Apr 2011 (estimated)
Results: Posted 22 May 2017

Clinical summary

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

Detailed description

Study design

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

Arm	Type	Receives
Exercise-induced PAH	Other	Drug: AmbrisentanOpen-label ambrisentan

Who may qualify

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

Key inclusion criteria (6 listed)

The participant provides written informed consent before the commencement of any study related procedure.
The participant is 18 years of age or older.
If a female participant of child-bearing potential, the participant must agree to use 2 forms of contraceptive therapy, including at least 1 barrier method, throughout the study and follow-up. (Women who are surgically sterile or those post-menopausal for at least 2 years are not considered to be of childbearing potential.)
The participant has findings of either exercise induced PAH on an Advanced Level-3 CPET performed within the last 6-months and is a New York Heart Association (NYHA) Class I or II.
The participant has a left ventricular ejection fraction (LVEF) of 55%, obtained by any appropriate method (i.e., echocardiographic assessment (ECHO), radionuclide imaging, or cardiac catheterization)

Key exclusion criteria (21 listed)

The participant has clinically significant psychiatric, addictive, neurologic disease or any other condition that, in the Investigator's opinion, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol.
The participant has evidence of unstable cardiovascular disease including intermittent atrial fibrillation or unstable angina within the 4 weeks prior to Screening.
The participant has diagnosis of exercise induced heart failure with preserved ejection fraction (previously diastolic dysfunction).
The participant has amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
The participant has a history of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention within the last 3 months.

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
AmbrisentanAlso: Letairis5 mg orally every day for 4 weeks. At Week 4, if ambrisentan 5 mg was tolerated, the dose was increased to 10 mg every day for the remainder of the 24-week period.	Drug	Exercise-induced PAH

Primary outcome

Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)
Time frame: Baseline to Week 24
mPAP is measure of the blood pressure found in the main artery of the lung. TPG is the difference between mean pulmonary arterial pressure and left atrial pressure. PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.
Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)
Time frame: Baseline to Week 24
PVR is the resistance offered by the pulmonary circulatory system.
Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )
Time frame: Baseline to Week 24
PVC is a measure of a pulmonary vein's ability to expand.
Change From Baseline in Peak Exercise Cardiac Output (CO)
Time frame: Baseline to Week 24
CO is the amount of blood pumped by the heart per minute.
Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max)
Time frame: Baseline to Week 24
VO2max is the measurement of the maximum amount of oxygen that an individual can utilize during intense or maximal exercise.

3 secondary outcomes

Change From Baseline in 6-minute Walk Distance (6MWD)
Time frame: Baseline to Week 24
Borg Dyspnea Scale Score
Time frame: Baseline and Week 24
World Health Organization Functional Class (WHO FC)
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 22 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exercise-induced PAH	30	22

Primary outcome: Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: mmHg

Measure	Exercise-induced PAH n = 22
mPAP	-5.2 (5.6)
TPG	-7.1 (8.0)
PCWP	2.9 (5.6)

Population analysed: The analysis population included evaluable participants who completed the 24-week treatment period.

Primary outcome: Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: Woods units (WU)

Measure	Exercise-induced PAH n = 22
Value	-0.9 (0.7)

Population analysed: The analysis population included evaluable participants who completed the 24-week treatment period.

Primary outcome: Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: mL/mmHg

Measure	Exercise-induced PAH n = 22
Value	0.8 (1.4)

Population analysed: The analysis population included evaluable participants who completed the 24-week treatment period.

Primary outcome: Change From Baseline in Peak Exercise Cardiac Output (CO)

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: L/min

Measure	Exercise-induced PAH n = 22
Value	2.3 (1.4)

Population analysed: The analysis population included evaluable participants who completed the 24-week treatment period.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exercise-induced PAH	0 of 30 (0%)	25 of 30 (83.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Exercise-induced Pulmonary Arterial Hypertension

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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.

Aaron Waxman, MD, PhD principal investigator

Brigham and Women's Hospital

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ambrisentan in people with Exercise-induced Pulmonary Arterial Hypertension, run by Brigham and Women's Hospital 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 6 inclusion and 21 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 18 Jan 2022. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 22 May 2017). 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?

Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP) (time frame: Baseline to Week 24). The study lists 5 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 NCT01338636.

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 18 Jan 2022.