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ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis (ARTEMIS-PH)

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ClinicalTrials.gov Identifier: NCT00879229
Recruitment Status : Terminated
First Posted : April 9, 2009
Results First Posted : April 22, 2014
Last Update Posted : May 15, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE April 8, 2009
First Posted Date  ICMJE April 9, 2009
Results First Submitted Date  ICMJE August 9, 2013
Results First Posted Date  ICMJE April 22, 2014
Last Update Posted Date May 15, 2014
Study Start Date  ICMJE July 2009
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
Change From Baseline in Six-minute Walk Distance (6MWD). [ Time Frame: Baseline to Week 16 ]
The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2009)
Change from baseline in six-minute walk distance (6MWD). [ Time Frame: 16 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Long-term Survival [ Time Frame: Week 48 ]
    Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.
  • Transition Dyspnea Index (TDI) [ Time Frame: Baseline to Week 16 ]
    The change in TDI at Week 16 (end of blinded treatment) was evaluated. TDI measures the change from the baseline characteristic "Baseline Dyspnea Index." The TDI range is -9 to +9 (worst to best; 0 = no change).
  • Change From Baseline in WHO Functional Class [ Time Frame: Baseline to Week 16 ]
    WHO functional class rates severity of pulmonary hypertension, with 4 categories on a scale of 1 to 4 with the worst category being 4. Change is represented as an increase ("+1: Improved"), decrease ("-1: Deteriorated"), or no change ("0: No change") on the scale.
  • Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted [ Time Frame: Baseline to Week 16 ]
    FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition.
  • Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline to Week 16 ]
    Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.
  • Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise [ Time Frame: Baseline to Week 16 ]
    Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
  • Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted [ Time Frame: Baseline to Week 16 ]
    DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient 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 as Assessed by the Short-Form 36® (SF-36) [ Time Frame: Baseline to Week 16 ]
    Each SF-36 score is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. An increase in score indicates an improvement in health state.
  • Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ) [ Time Frame: Baseline to Week 16 ]
    The SRGQ is designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency & severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2009)
  • Long-term survival [ Time Frame: 48 weeks ]
  • Borg Dyspnea Index [ Time Frame: 16 weeks ]
  • WHO Functional Class [ Time Frame: 16 weeks ]
  • Pulmonary Function Tests (FVC and DLCO) [ Time Frame: 16 weeks ]
  • BDI/TDI [ Time Frame: 16 weeks ]
  • Quality of Life assessments [ Time Frame: 16 weeks ]
  • NT-proBNP [ Time Frame: 16 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension
Brief Summary Ambrisentan is an endothelin receptor antagonist used for the treatment of pulmonary hypertension (PH). Based on research suggesting a role for endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the poor prognosis for patients with IPF who are also diagnosed with PH, this study was designed to evaluate the effectiveness and safety of ambrisentan in that patient population.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Idiopathic Pulmonary Fibrosis
  • Pulmonary Hypertension
Intervention  ICMJE
  • Drug: Ambrisentan
    Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.
    Other Name: Letairis
  • Drug: Placebo
    Placebo to match ambrisentan administered orally once daily.
Study Arms  ICMJE
  • Experimental: Ambrisentan
    Participants were randomized to receive ambrisentan treatment at an initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 52 weeks
    Intervention: Drug: Ambrisentan
  • Placebo Comparator: Placebo
    Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.
    Interventions:
    • Drug: Ambrisentan
    • Drug: Placebo
Publications * Ruocco G, Cekorja B, Rottoli P, Refini RM, Pellegrini M, Di Tommaso C, Del Castillo G, Franci B, Nuti R, Palazzuoli A. Role of BNP and echo measurement for pulmonary hypertension recognition in patients with interstitial lung disease: An algorithm application model. Respir Med. 2015 Mar;109(3):406-15. doi: 10.1016/j.rmed.2014.12.011. Epub 2015 Jan 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 11, 2011)
40
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2009)
220
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Selected Inclusion Criteria:

  • Weight ≥ 40 kg at screening
  • Diagnosis of IPF based on modified American Thoracic Society-European Respiratory Society guidelines
  • Diagnosis of PH based on the following hemodynamic requirements: mean pulmonary artery pressure (mPAP ≥ 25 mm Hg; pulmonary vascular resistance > 240 dyne.sec/cm^5; pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mm Hg
  • Forced vital capacity (FVC) ≥ 40%
  • Able to walk at least 50 meters during two 6-minute walk tests
  • If receiving calcium channel blockers, low-dose oral corticosteroids, immunosuppressive, cytoxic, or antifibrotic drugs dose must have been stable.

Selected Exclusion Criteria:

  • Diagnosis of PH primarily due to an etiology other than IPF
  • Surgical lung biopsy diagnosis other than Usual Interstitial Pneumonia
  • Other known cause of interstitial lung disease
  • Evidence of significant obstructive lung disease
  • Recent hospitalization for an acute exacerbation of IPF
  • Recent active pulmonary or upper respiratory tract infection
  • Left ventricular ejection fraction < 40%
  • Serum creatinine ≥ 2.5 mg/dL
  • Required hemodialysis, peritoneal dialysis, or hemofiltration
  • Female subject who was pregnant or breastfeeding
  • Recent treatment for PH with an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, or prostacyclin derivative
  • Recent treatment with high dose oral corticosteroids
  • Recent treatment (within 4 weeks prior to screening) with imatinib mesylate (Gleevec)
  • Alanine aminotransferase or aspartate aminotransferase lab value that was greater than 1.5 x the upper limit of the normal range
  • Discontinued other ERA treatment for any adverse reaction other than those associated with liver function test abnormalities
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   Germany,   Italy,   United Kingdom,   United States
Removed Location Countries Belgium,   Ireland,   Israel
 
Administrative Information
NCT Number  ICMJE NCT00879229
Other Study ID Numbers  ICMJE GS-US-300-0128
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Gilead Sciences
Original Responsible Party Sarah Gilroy, Senior Clinical Program Manager, Gilead Sciences
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hunter Gillies, M.D. Gilead Sciences
PRS Account Gilead Sciences
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP