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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
224
Oral tablets taken once daily.
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
Time frame: Baseline to Week 24
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.
Time frame: 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.
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
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.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Arizona Pulmonary Specialists, Ltd
Phoenix, Arizona, United States
UCSD Medical Center, Thornton Hospital
La Jolla, California, United States
Greater Los Angeles, VA Medical Center
Los Angeles, California, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, United States
University of Colorado Health Sciences Center
Aurora, Colorado, United States
University of Connecticut Health Center
Farmington, Connecticut, United States
Pulmonary Hypertension Clinic Mount Sinai Medical Center
Miami Beach, Florida, United States
Suncoast Lung Center
Sarasota, Florida, United States
Medical College of Georgia
Augusta, Georgia, United States
...and 29 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to Week 48
Monotherapy Treatment Status
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Time frame: Baseline to Week 24
Monotherapy Treatment Status
Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Time frame: Baseline to Week 48
Long-term Survival
Defined as not dying during study participation
Time frame: Baseline to Week 24
Long-term Survival
Defined as not dying during study participation
Time frame: Baseline to Week 48