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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00712166




Registration number
NCT00712166
Ethics application status
Date submitted
7/07/2008
Date registered
9/07/2008
Date last updated
20/12/2010

Titles & IDs
Public title
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa
Scientific title
A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine For Inhalation in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4)
Secondary ID [1] 0 0
GS-US-205-0117
Universal Trial Number (UTN)
Trial acronym
AIR-CF4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Lung Infection 0 0
Pseudomonas Aeruginosa 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Placebo comparator: Placebo three times daily (TID) -

Experimental: AZLI 75 mg three times daily (TID) -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28
Assessment method [1] 0 0
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [1] 0 0
Day 0 to Day 28
Secondary outcome [1] 0 0
Change From Baseline in CFQ-R RSS Score at Day 14
Assessment method [1] 0 0
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [1] 0 0
Day 0 to Day 14
Secondary outcome [2] 0 0
Change From Baseline in CFQ-R RSS Score at Day 42
Assessment method [2] 0 0
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [2] 0 0
Day 0 to Day 42
Secondary outcome [3] 0 0
Change From Baseline in CFQ-R Physical Functioning Domain Score
Assessment method [3] 0 0
The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0 (baseline), 14, 28, and 42 (the last study visit). The endpoint was change from baseline in the physical functioning domain (e.g., ability to walk and engage in physical activities) of the CFQ-R at Day 28 (range of scores: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R physical functioning domain score and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [3] 0 0
Day 0 to Day 28
Secondary outcome [4] 0 0
Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study
Assessment method [4] 0 0
The number of participants requiring additional antipseudomonal antibiotics (oral, intravenous \[IV\], or by inhalation), the time to use of these antibiotics, and the reasons for use was recorded. A binary variable was defined to indicate whether the participants needed any antipseudomonal antibiotics that were non-study drug via the oral, IV, or inhalation route between Day 0 (Baseline Visit) and Day 42 (Visit 5). Fisher's Exact Test was implemented on the intent-to-treat (ITT) and per protocol analysis sets to detect treatment effects on need for additional antipseudomonal antibiotics.
Timepoint [4] 0 0
Day 0 to Day 42
Secondary outcome [5] 0 0
Number of Participants Hospitalized During Study
Assessment method [5] 0 0
Hospitalization was defined as any hospital admission lasting for more than 1 calendar day that had been recorded as a serious adverse event (SAE) on the electronic case report form (eCRF). Binary variables were defined to indicate whether participants experienced any hospitalization. Number of hospitalizations was summarized by treatment group.
Timepoint [5] 0 0
Day 0 to Day 42
Secondary outcome [6] 0 0
Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28
Assessment method [6] 0 0
Sputum samples were collected at all study visits for quantitative and qualitative culture for PA. Sputum PA density was quantified by logarithm transformation of the CFU value with base 10. Change from baseline in sputum PA density was calculated as the difference between the log10 CFU values at Day 28 (Visit 4) and the baseline value. Missing data was not imputed. Baseline log10 CFU and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [6] 0 0
Day 0 to Day 28
Secondary outcome [7] 0 0
Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted
Assessment method [7] 0 0
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested by the ANCOVA model using the ITT analysis set. Baseline FEV1 percent predicted and age group (\<18 vs. \>=18 years) were included as covariates in the analysis.
Timepoint [7] 0 0
Day 0 to Day 28

Eligibility
Key inclusion criteria
* Participants = 6 years of age
* Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

* Sweat chloride = 60 mEq/L by quantitative pilocarpine iontophoresis test
* Two well characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
* Abnormal nasal potential difference
* PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1 (one of the previous PA positive cultures must have been no more than 3 months prior to Visit 1)
* FEV1 > 75% predicted at Visit 1
* Participants must have exhibited two or more of the following chronic and/or intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:

* Chest congestion
* Daily cough
* Productive cough
* Wheezing
* Trouble breathing
* Nocturnal wakening due to coughing
* Participants (and parent/guardian as required) had to be able to provide written informed consent/assent prior to any study related procedures
* Females of childbearing potential had to have a negative urine pregnancy test at Visit 1
* Ability to perform reproducible pulmonary function tests
* In the opinion of the Investigator, the participant did not require immediate antipseudomonal antibiotic intervention to treat an impending exacerbation, and the participant's condition was stable enough to enroll in the study
Minimum age
6 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Administration of any investigational drug or device within 28 days prior to Visit 1 or within 6 half-lives of the investigational drug (whichever was longer)
* Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days prior to Visit 1
* Known local or systemic hypersensitivity to monobactam antibiotics
* Inability to tolerate short-acting bronchodilator (BD) use at least TID
* Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
* Changes in or initiation of chronic hypertonic saline treatment within 28 days prior to Visit 1
* Changes in or initiation of dornase alfa within 28 days prior to Visit 1
* Changes in antimicrobial, BD, or corticosteroid medications within 7 days prior to Visit 1
* Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
* History of lung transplantation
* History of participation (enrollment) in any prior clinical studies with AZLI
* A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with abnormalities indicating a significant acute finding (e.g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and interpreted between Visits 1 and 2 was also acceptable for determining eligibility
* Positive urine pregnancy test at Visit 1; all women of childbearing potential were to be tested
* Females of childbearing potential who were lactating or were not (in the opinion of the investigator) practicing an acceptable method of birth control; female participants who utilized hormonal contraceptives as their birth control method must have used the same method for at least 3 months before study dosing
* Participant was being assessed at Visit 1 by the investigator for an acute change in respiratory symptoms
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would have interfered with participant treatment, assessment, or compliance with the protocol

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2009
Sample size
Target
Accrual to date
Final
160
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Department of Respiratory Medicine, The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Department of Respiratory Medicine, Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
The Prince Charles Hospital, Adult Cystic Fibrosis Centre - Chermside
Recruitment hospital [4] 0 0
Respiratory Medicine, Royal Children's Hospital - Herston
Recruitment hospital [5] 0 0
Child and Adolescent Health Services, Princess Margaret Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Chermside
Recruitment postcode(s) [3] 0 0
- Herston
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
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
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
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
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Claire Wainwright, MD
Address 0 0
Royal Children's Hospital, Brisbane, QLD, Australia
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00712166