(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
The ARTEMIS-IPF study was conducted to determine if ambrisentan was effective in delaying disease progression and death in participants with idiopathic pulmonary fibrosis (IPF), to evaluate its safety, and to evaluate its effect on development of pulmonary hypertension, quality of life, and dyspnea (shortness of breath) symptoms in this participant population. Participants were randomized in a 2:1 ratio to receive ambrisentan or placebo, respectively. Participation in the study was to be up to 4 years, depending on how long it would take to enroll participants and observe study events. After randomization, visits to the clinic took place every 3 months, and laboratory procedures were performed every month.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||ARTEMIS-IPF: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Early Idiopathic Pulmonary Fibrosis (IPF)|
- Time to Death or Disease (IPF) Progression. [ Time Frame: Up to 48 months ] [ Designated as safety issue: No ]
The median time to death or disease progression was based on Kaplan-Meier (KM) estimates of pooling over strata, and was defined as the first occurrence of any of the following:
- Either 1) a decrease of ≥ 10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg), or 2) a decrease of ≥ 5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days
- Respiratory hospitalization (hospitalization involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxemia, or radiographic findings on chest x-ray or high-resolution computerised tomography (HRCT) scan
- All-cause mortality
- Proportion of Participants With No Disease Progression or Death at 48 Weeks [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The proportion of participants with no disease progression or death is presented as a percentage using a Kaplan-Meier (KM) estimate of survival or not experiencing disease progression.
- Change in FVC % Predicted at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]FVC is defined as the volume of air (liters) that can forcibly be blown out after taking a full breath. FVC % predicted is defined as FVC % of the participant divided by the average FVC % in the population for any person of similar age, sex, and body composition.
- Change in DLCO % Predicted at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood. DLCO % predicted is defined as DLCO % of the participant divided by the average DLCO % in the population for any person of similar age, sex and body composition.
- Change in 6MWT at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The 6MWT is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.
- Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state.
- Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The SGRQ is designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airways disease. The range of each score is 0-100, with 0 indicating fewer limitations and 100 indicating more limitations; an increase in score indicates an increase in limitations.
- Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A TDI score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests.
- Percentage of Participants Who Developed PH on Study [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]The percentage of participants known to have developed pulmonary hypertension on study documented by right heart catheterization (RHC) was analyzed. RHC was done at baseline and 48 weeks, or at the early termination visit.
|Study Start Date:||December 2008|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Ambrisentan (5mg or 10 mg tablet) was administered orally once daily.
Other Name: Letairis®
|Placebo Comparator: Placebo||
Placebo to match ambrisentan was administered orally once daily.
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|Study Chair:||Ganesh Raghu, MD||University of Washington, Div. of Pulmonary and Critical Care Medicine Chair|