(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Ambrisentan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females from 40 to 80 years of age Diagnosis of IPF Honeycombing (fibrosis in the lung) on high-resolution computerised tomography (HRCT) scan of less than or equal to 5% Willing and able to have 2 right heart catheterizations performed Willing to have monthly lab tests to monitor liver function Able to perform the 6 minute walk test (indicated adequate physical function) Must have meet lung function requirements Normal liver function tests Negative serum pregnancy test Willing to use at least 2 reliable methods of contraception Able to understand and willing to sign informed consent form Exclusion Criteria: No restrictive lung disease (other than usual interstitial pneumonia or IPF) No obstructive lung disease No recent or active respiratory exacerbations No recent hospitalization for an IPF exacerbation No recent history of alcohol abuse Chronic sildenafil (or same drug class) use for pulmonary hypertension Chronic treatment with certain medications for IPF within 30 days of randomization No other serious medical conditions

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ambrisentan<br> | Drug: Ambrisentan<br>* Ambrisentan (5mg or 10 mg tablet) was administered orally once daily.<br>* Other names: Letairis®;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo to match ambrisentan was administered orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Death or Disease (IPF) Progression. | 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 | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With No Disease Progression or Death at 48 Weeks | 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. | Baseline and Week 48 | 
| Change in FVC % Predicted at Week 48 | 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. | Baseline and Week 48 | 
| Change in DLCO % Predicted at Week 48 | 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. | Baseline and Week 48 | 
| Change in 6MWT at Week 48 | 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. | Baseline and Week 48 | 
| Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36) | 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. | Baseline and Week 48 | 
| Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ) | 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. | Baseline and Week 48 | 
| Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI) | 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. | Baseline and Week 48 | 
| Percentage of Participants Who Developed PH on Study | 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. | Up to 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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idiopathic pulmonary fibrosis, interstitial lung disease, ambrisentan