Please note that the ANZCTR website will be unavailable from 1pm until 2pm (AEST) on Wednesday 29th May for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00879229




Registration number
NCT00879229
Ethics application status
Date submitted
8/04/2009
Date registered
8/04/2009
Date last updated
5/05/2014

Titles & IDs
Public title
ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
Scientific title
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
Secondary ID [1] 0 0
GS-US-300-0128
Universal Trial Number (UTN)
Trial acronym
ARTEMIS-PH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Pulmonary Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ambrisentan
Treatment: Drugs - Placebo

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

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.


Treatment: Drugs: Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.

Treatment: Drugs: Placebo
Placebo to match ambrisentan administered orally once daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Six-minute Walk Distance (6MWD). - The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [1] 0 0
Long-term Survival - Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Transition Dyspnea Index (TDI) - 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).
Timepoint [2] 0 0
Baseline to Week 16
Secondary outcome [3] 0 0
Change From Baseline in WHO Functional Class - 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.
Timepoint [3] 0 0
Baseline to Week 16
Secondary outcome [4] 0 0
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted - 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.
Timepoint [4] 0 0
Baseline to Week 16
Secondary outcome [5] 0 0
Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) - Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.
Timepoint [5] 0 0
Baseline to Week 16
Secondary outcome [6] 0 0
Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise - 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).
Timepoint [6] 0 0
Baseline to Week 16
Secondary outcome [7] 0 0
Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted - 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.
Timepoint [7] 0 0
Baseline to Week 16
Secondary outcome [8] 0 0
Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36) - 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.
Timepoint [8] 0 0
Baseline to Week 16
Secondary outcome [9] 0 0
Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ) - 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.
Timepoint [9] 0 0
Baseline to Week 16

Eligibility
Key inclusion criteria
Selected

- 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
Minimum age
35 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
St. Vincents Hospital - Sydney
Recruitment hospital [2] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maine
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
New Hampshire
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Utah
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Washington
Country [27] 0 0
Austria
State/province [27] 0 0
Graz
Country [28] 0 0
Austria
State/province [28] 0 0
Innsbruck
Country [29] 0 0
Austria
State/province [29] 0 0
Vienna
Country [30] 0 0
Canada
State/province [30] 0 0
Alberta
Country [31] 0 0
Canada
State/province [31] 0 0
British Columbia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Donaustauf
Country [36] 0 0
Germany
State/province [36] 0 0
Freiburg
Country [37] 0 0
Germany
State/province [37] 0 0
Greifswald
Country [38] 0 0
Germany
State/province [38] 0 0
Hannover
Country [39] 0 0
Germany
State/province [39] 0 0
Heidelberg
Country [40] 0 0
Germany
State/province [40] 0 0
Munchen
Country [41] 0 0
Italy
State/province [41] 0 0
Catania
Country [42] 0 0
Italy
State/province [42] 0 0
Forli
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Milan
Country [45] 0 0
Italy
State/province [45] 0 0
Padova
Country [46] 0 0
Italy
State/province [46] 0 0
Palermo
Country [47] 0 0
Italy
State/province [47] 0 0
Rome
Country [48] 0 0
Italy
State/province [48] 0 0
Siena
Country [49] 0 0
Italy
State/province [49] 0 0
Torino
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Cambridge
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Liverpool
Country [52] 0 0
United Kingdom
State/province [52] 0 0
London
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00879229
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hunter Gillies, M.D.
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00879229