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

Phase 3
Terminated
Conditions
Idiopathic Pulmonary Fibrosis
Interventions
Drug: Placebo
Registration Number
NCT00768300
Lead Sponsor
Gilead Sciences
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
494
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
AmbrisentanAmbrisentan-
Primary Outcome Measures
NameTimeMethod
Time to Death or Disease (IPF) Progression.Up to 48 months

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

Secondary Outcome Measures
NameTimeMethod
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)Baseline and Week 48

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.

Proportion of Participants With No Disease Progression or Death at 48 WeeksBaseline and Week 48

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 6MWT at Week 48Baseline and 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.

Change in FVC % Predicted at Week 48Baseline and 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.

Change in DLCO % Predicted at Week 48Baseline and 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.

Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)Baseline and Week 48

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)Baseline and Week 48

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 StudyUp to 48 weeks

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.

Trial Locations

Locations (27)

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

University of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Bay Area Chest Physicians

🇺🇸

Clearwater, Florida, United States

Pulmonary Associates

🇺🇸

Phoenix, Arizona, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

The Oregon Clinic, P.C.

🇺🇸

Portland, Oregon, United States

National Jewish Medical And Research Center

🇺🇸

Denver, Colorado, United States

University of Miami Miller School of Medicine

🇺🇸

Miami, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Alabama at Birmingham Hospital

🇺🇸

Birmingham, Alabama, United States

David Geffen School of Medicine at UCLA(Harbor-UCLA Medical Center)

🇺🇸

Los Angeles, California, United States

Stanford University

🇺🇸

Stanford, California, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Saint Lukes Foundation

🇺🇸

Chesterfield, Missouri, United States

Dartmouth Medical School

🇺🇸

Lebanon, New Hampshire, United States

Pulmonary & Allergy Associates

🇺🇸

Summit, New Jersey, United States

Pulmonary And Critical Care Services, P.C.

🇺🇸

Albany, New York, United States

Winthrop University Hospital

🇺🇸

Mineola, New York, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

University of Pennsylvania Health Systems

🇺🇸

Philadelphia, Pennsylvania, United States

The Reading Hospital and Medical Center

🇺🇸

Reading, Pennsylvania, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Complejo Asistencial Universitario de León

🇪🇸

Leon, Castilla, Spain

Hospital Virgen del Rocio

🇪🇸

Sevilla, Andalucia, Spain

Kentuckiana Pulmonary Association

🇺🇸

Louisville, Kentucky, United States

University of California, Davis

🇺🇸

Sacramento, California, United States

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