Pulmonary HypertensionPhase 3NCT00380068
Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
A Phase 3 study testing Ambrisentan in people with Pulmonary Hypertension, run by Gilead Sciences at 39 sites in 3 countries.
Trial summary
The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary 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
- 224 participants
- Where
- 39 sitesin 3 countries
- Study dates
- Aug 2006to May 2009
- Phase
- Phase 3
- 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
Summarized Inclusion Criteria:
- 18 years of age or older
- Current diagnosis of PH associated with an acceptable etiology as outlined in the protocol, including: PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5).
- Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy
- Right heart catheterization completed prior to screening must meet pre-specified criteria
- Female participants of childbearing potential must have a negative serum pregnancy test and must agree to use a reliable double method of contraception until study completion and for at least four weeks following their final study visit.
- Male participants must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking ambrisentan and queried regarding his understanding of the potential risks as described in the Informed Consent Form.
Summarized Exclusion Criteria:
- Participation in a previous clinical study with ambrisentan
- Bosentan or sitaxsentan use within four weeks prior to the screening visit
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is greater than 3 times the upper limit of normal at the screening visit
- Pulmonary function tests not meeting the following pre-specified criteria: 1) mean pulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonary capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15 mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participants without ILD or >= 60% of predicted normal in participants with ILD; forced expiratory volume in 1 second (FEV1) >= 65% of predicted normal in participants without COPD or >= 50% of predicted normal in participants with COPD
- Contraindication to treatment with endothelin receptor antagonist (ERA)
- History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years
- Female participant who is pregnant or breastfeeding
Trial locations and contacts
39 sites in 3 countries.
39 sites in 3 countries
United States34 sites
Medical College of Georgia
Augusta, Georgia, 30912
University of Colorado Health Sciences Center
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Tufts-New England Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Adult Congenital Heart Service
Boston, Massachusetts, 02115
Boston University School of Medicine
Boston, Massachusetts, 02118
University of Virginia Health Sciences Center
Charlottesville, Virginia, 22908
University of Chicago Hospitals
Chicago, Illinois, 60637
The Lindner Clinical Trial Center
Cincinnati, Ohio, 45219
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Atlanta Institute for Medical Research, Inc.
Decatur, Georgia, 30030
Duke University Medical Center
Durham, North Carolina, 27710
University of Connecticut Health Center
Farmington, Connecticut, 06030
Baylor College of Medicine
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
UCSD Medical Center, Thornton Hospital
La Jolla, California, 92037
Lexington Pulmonary and Critical Care
Lexington, South Carolina, 29072
Greater Los Angeles, VA Medical Center
Los Angeles, California, 90073
Pulmonary Hypertension Clinic Mount Sinai Medical Center
Miami Beach, Florida, 33140
New York Presbyterian Pulmonary Hypertension Center
New York, New York, 10032
University of Medicine & Dentistry of New Jersey
Newark, New Jersey, 07103
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Arizona Pulmonary Specialists, Ltd
Phoenix, Arizona, 85013
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Pittsburgh Medical Center Presbyterian
Pittsburgh, Pennsylvania, 15213
Legacy Clinical Northwest
Portland, Oregon, 97210
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic
Rochester, Minnesota, 55905
Mary Parkes Asthma Center
Rochester, New York, 14623
Suncoast Lung Center
Sarasota, Florida, 34233
Washington University School of Medicine
St Louis, Missouri, 63110
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
Canada3 sites
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
University of Alberta Hospitals
Edmonton, Alberta, T6G 2B7
Toronto General Hospital
Toronto, Ontario, M5G 2N2
Australia2 sites
St. Vincent's Hospital
Darlinghurst, New South Wales, 2010
Royal Perth Hospital
Perth, 6000
About this study
Official title: ARIES-3: A Phase 3, Long-Term, Open-Label, Multicenter Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
Read the detailed description
This study was to enroll up to 200 participants with PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5). Participants with left heart disease or left heart failure were excluded (WHO Group 2). Participants could be receiving prostacyclin or sildenafil therapy at baseline, and participants who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities were eligible.
- Conditions
- Pulmonary Hypertension
- Being tested
- Ambrisentan
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called Letairis, Volibris
Oral tablets taken once daily.
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | Not described Receives: Drug: Ambrisentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
Measured: Baseline to Week 24
Secondary outcomes (16)
Change From Baseline to Week 24 in Borg Dyspnea Index
Change from Baseline to Week 24 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Measured: Baseline to Week 24
Change From Baseline to Week 48 in Borg Dyspnea Index
Change from Baseline to Week 48 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Measured: Baseline to Week 48
Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)
Measured: Baseline to Week 24
Percent Change From Baseline to Week 48 in BNP
Measured: Baseline to Week 48
Change From Baseline to Week 24 in WHO Functional Class
Change from baseline in World Health Organization functional class (WHO) at Week 24 is the incidence of participants that improved, had no change, or worsened. WHO categories are 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Measured: Baseline to Week 24
Change From Baseline to Week 48 in WHO Functional Class
Change from baseline in WHO at Week 48 is expressed as the incidence of participants that improved, had no change or worsened. WHO categories range from 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Measured: Baseline to Week 48
Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale
Change from baseline to Week 24 in the SF-36 health survey physical functioning scale. 10 activities rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General United States (US) population mean and standard deviation (SD). Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Measured: Baseline to Week 24
Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale
Change from baseline to Week 48 in the SF-36 health survey physical functioning scale. 10 activities are rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General US population mean and standard deviation. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and standard deviation of 10.
Measured: Baseline to Week 48
Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24
Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Measured: Baseline to Week 24
Percent of Participants With no Clinical Worsening of PH at Week 48
Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Measured: Baseline to Week 48
Failure-free Treatment Status
Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Measured: Baseline to Week 24
Failure-free Treatment Status
Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Measured: Baseline to Week 48
Monotherapy Treatment Status
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Measured: Baseline to Week 24
Monotherapy Treatment Status
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Measured: Baseline to Week 48
Long-term Survival
Defined as not dying during study participation
Measured: Baseline to Week 24
Long-term Survival
Defined as not dying during study participation
Measured: Baseline to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2006 (estimated)
- Study startAug 2006
- Primary completionJul 2008
- Study completionMay 2009
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 Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lewis J Rubin, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00380068
- Sponsor's protocol ID
- AMB-323
- Other IDs
- ARIES-3
- Status last verified
- Apr 2012
- First submitted
- 21 Sep 2006
- Last updated
- 5 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ARIES-3: A Phase 3, Long-Term, Open-Label, Multicenter Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT00380068
- Acronym / sponsor ID
- AMB-323
- Conditions
- Pulmonary Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Jul 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 25 Sep 2006 (estimated)
- Results
- Posted 19 Nov 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
Detailed description
This study was to enroll up to 200 participants with PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5). Participants with left heart disease or left heart failure were excluded (WHO Group 2). Participants could be receiving prostacyclin or sildenafil therapy at baseline, and participants who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities were eligible.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: Ambrisentan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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: Letairis, VolibrisOral tablets taken once daily. | Drug | Ambrisentan |
Primary outcome
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
Time frame: Baseline to Week 24
16 secondary outcomes
Change From Baseline to Week 24 in Borg Dyspnea Index
Time frame: Baseline to Week 24
Change From Baseline to Week 48 in Borg Dyspnea Index
Time frame: Baseline to Week 48
Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)
Time frame: Baseline to Week 24
Percent Change From Baseline to Week 48 in BNP
Time frame: Baseline to Week 48
Change From Baseline to Week 24 in WHO Functional Class
Time frame: Baseline to Week 24
Change From Baseline to Week 48 in WHO Functional Class
Time frame: Baseline to Week 48
Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale
Time frame: Baseline to Week 24
Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale
Time frame: Baseline to Week 48
Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24
Time frame: Baseline to Week 24
Percent of Participants With no Clinical Worsening of PH at Week 48
Time frame: Baseline to Week 48
Failure-free Treatment Status
Time frame: Baseline to Week 24
Failure-free Treatment Status
Time frame: Baseline to Week 48
Monotherapy Treatment Status
Time frame: Baseline to Week 24
Monotherapy Treatment Status
Time frame: Baseline to Week 48
Long-term Survival
Time frame: Baseline to Week 24
Long-term Survival
Time frame: Baseline to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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.
Lewis J Rubin, MD principal investigator
University of California, San Diego
39 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ambrisentan in people with Pulmonary Hypertension, run by Gilead Sciences at 39 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 5 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Canada, Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 19 Nov 2010). 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 to Week 24 in 6 Minute Walk Distance (6MWD) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Apr 2012.