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Pulmonary Arterial HypertensionPhase 4ATHENA-1NCT00617305

Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)

A Phase 4 study testing Ambrisentan, Sildenafil and Tadalafil in people with Pulmonary Arterial Hypertension, run by Gilead Sciences at 30 sites 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

To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to… Read more about this study

Who is it for?
Ages 16 to 75 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Ambrisentan, Sildenafil and Tadalafil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
38 participants
Where
30 sitesUnited States
Study dates
Apr 2008to Jul 2011
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 16 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Selected Inclusion Criteria

  • Must be between 16 and 75 years of age;
  • Must weigh at least 40 kg;
  • Have a current diagnosis of idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or human immunodeficiency virus (HIV);
  • Have WHO functional class III symptoms;
  • Be receiving sildenafil or tadalafil monotherapy for the treatment of PAH for at least the past 12 weeks and at a stable dose for at least 8 consecutive weeks;
  • Meet all of the following hemodynamic criteria by means of a right heart catheterization: mPAP of at least 25 mmHg; PVR of at least 400 dyne*sec/cm5; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of not more than 15 mmHg;
  • Meet all of the following pulmonary function test criteria no more than 12 weeks before the screening visit: total lung capacity at least 60% of predicted normal and forced expiratory volume in 1 second of at least 65% of predicted normal;
  • Able to walk at least 150 meters during the screening 6-minute walk test (6MWT);
  • If receiving calcium channel blockers or 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins) must be on stable therapy for at least 4 weeks;
  • If diagnosed with HIV, must have stable disease status.

Selected Exclusion Criteria:

  • Have a current pulmonary hypertension diagnosis other than idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or HIV;
  • Have left ventricular ejection fraction (LVEF) ≤40% or clinically significant ischemic, valvular, or constrictive heart disease;
  • Have received chronic prostanoid or endothelin receptor antagonist (ERA) therapy (eg, bosentan, sitaxsentan) within the past 12 weeks;
  • Have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities;
  • Have received IV inotropes within 2 weeks;
  • Have a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is greater than 2.0x the upper limit of normal.

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

United States30 sites

  • Asheville Cardiology Associates

    Asheville, North Carolina, 28803

  • Emory University

    Atlanta, Georgia, 30322

  • University of Maryland

    Baltimore, Maryland, 21201

  • BACH Cardiology

    Boston, Massachusetts, 02115

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • The Lindner Clinical Trial Center

    Cincinnati, Ohio, 45219

  • University Hospitals of Cleveland

    Cleveland, Ohio, 44106

  • Ohio State University

    Columbus, Ohio, 43210

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

  • Atlanta Institute for Medical Research

    Decatur, Georgia, 30030

  • Wayne State University

    Detroit, Michigan, 48201

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Cleveland Clinic

    Fort Lauderdale, Florida, 33331

  • University of Florida

    Gainesville, Florida, 32610

  • Baylor College of Medicine

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • West Los Angeles Healthcare Center

    Los Angeles, California, 90073

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • University of South Alabama

    Mobile, Alabama, 36617

  • Weill Cornell Medical Center

    New York, New York, 10021

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Orlando Heart Center

    Orlando, Florida, 32806

  • Arizona Pulmonary Specialists

    Phoenix, Arizona, 85013

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Scott & White Memorial Hospital

    Temple, Texas, 76508

  • Harbor - UCLA

    Torrance, California, 90502

Other trials in United States

About this study

Official title: An Open-label, Multicenter Study of Ambrisentan and a Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects With Pulmonary Arterial Hypertension Who Have Demonstrated a Sub-Optimal Response to a Phosphodiesterase Type-5 Inhibitor

To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.

Read the detailed description

The primary objective of this study is to evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.

Being tested
Ambrisentan, Placebo, Sildenafil, Tadalafil
Keywords
ambrisentan, PAH, combination therapy, phosphodiesterase type-5 inhibitor (PDE-5i), cardiovascular, endothelin receptor antagonist, ERA
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

    Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.

  • PlaceboDrug

    Placebo to match ambrisentan was administered orally once daily.

  • SildenafilDrug

    Also called Revatio, Viagra

    Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.

  • TadalafilDrug

    Also called Cialis, Adcirca

    Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.

Study groups in NCT00617305
Study groupRoleWhat they receive
AmbrisentanExperimentalPatients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i; sildenafil or tadalafil).
Receives: Drug: Ambrisentan; Drug: Sildenafil; Drug: Tadalafil
PlaceboActive comparatorPatients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (sildenafil or tadalafil).
Receives: Drug: Placebo; Drug: Sildenafil; Drug: Tadalafil

What is being measured

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

  1. Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)

    The primary objective of this study is to evaluate the change from baseline in PVR, and other hemodynamic parameters, following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy. A decrease in measurement value (dynes sec/cm^5) indicates improvement for this patient population.

    Measured: Baseline to Week 24

Secondary outcomes (10)

  1. Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)

    This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.

    Measured: Baseline to Week 24

  2. Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)

    This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.

    Measured: Baseline to Week 24

  3. Change From Baseline in Cardiac Output (LOCF)

    This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population.

    Measured: Baseline to Week 24

  4. Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

    The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. An increase in measurement value (meters walked) indicates improvement for this patient population.

    Measured: Baseline to Week 48

  5. Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

    The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. The dyspnea index measures the degree of breathlessness after completion of the 6MWT using a scale of 0 to 10, with 0 indicating no breathlessness and 10 indicating maximum breathlessness.

    Measured: Baseline to Week 48

  6. Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)

    The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 12, 36, and 48 were also evaluated. Lower scores and decreases from baseline represent improved functioning and QOL. The CAMPHOR survey was not assessed at Week 4. The total CAMPHOR score scale ranges from 0 (good) to 25 (poor). A reduction in score over time represents improvement in this patient population.

    Measured: Baseline to Week 48

  7. Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.

    The primary analysis of this secondary outcome measure is change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. WHO categories are 1 to 4 with the worst category being 4. Improvement is represented by a change in category to a lower number (for example, change from category 3 to 2), and deterioration is represented by a change in category to a higher number (for example, change from category 2 to 4). No change is represented by no change in category (for example, category 2 which remains 2).

    Measured: Baseline to Week 48

  8. Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

    The primary analysis of this secondary outcome measure is mean percent change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. A decrease in log-transformed measurement value (pg/mL) indicates improvement for this patient population.

    Measured: Baseline to Week 48

  9. Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48

    The time to clinical worsening was defined as the time from enrollment to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, or initiation of chronic parenteral prostanoid therapy. Results are presented as the Kaplan-Meier estimate (% probability) of having clinical worsening after a given time.

    Measured: Baseline to Week 48+

  10. Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48

    Overall survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of death after a given time.

    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.

  1. First posted18 Feb 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionFeb 2011
  4. Study completionJul 2011

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00617305
Sponsor's protocol ID
GS-US-300-0117
Acronym
ATHENA-1
Status last verified
Jun 2012
First submitted
6 Feb 2008
Last updated
30 Jul 2012
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ambrisentan, Sildenafil and Tadalafil in people with Pulmonary Arterial Hypertension, run by Gilead Sciences at 30 sites 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?

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 30 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites 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 30 Jul 2012). 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 in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) (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?

On the ClinicalTrials.gov record for NCT00617305.

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 30 Jul 2012.

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