Back to resultsInternational Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (AIR-CF1)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AZLI 75 mg three times a day (TID)
Placebo three times a day (TID)
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, Pseudomonas aeruginosa, Pulmonary Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria: 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 greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT); Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or Abnormal nasal potential difference. PA present in expectorated sputum or throat swab culture at Screening. FEV1 between (and including) 25% and 75% predicted at Screening. Negative pregnancy test at Screening. Ability to perform reproducible pulmonary function tests. Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening. Ability to provide written informed consent. Exclusion Criteria: Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening. Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day. History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years. History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night. Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer). Known local or systemic hypersensitivity to monobactam antibiotics. Inability to tolerate short-acting bronchodilator use at least three times daily. Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit. Changes in physiotherapy technique or schedule within 7 days prior to Screening or between Screening and the next visit. History of lung transplantation. A chest x-ray indicating abnormal findings at Screening or within the previous 90 days. Abnormal renal or hepatic function at Screening. 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. Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.
Sites / Locations
- University of Alabama at Birmingham
- Pediatric Breathing Disorders Clinic
- Phoenix Children's Hospital
- University of Arkansas for Medical Sciences
- Miller Children's Hospital
- Children's Hospital, Los Angeles
- Children's Hospital of Orange County
- Capital Allergy and Respiratory Disease Center
- Yale New Haven Hospital
- University of Florida Health Sciences Center
- Nemours Children's Clinic, Orlando
- Medical College of Georgia
- Children's Memorial Hospital / Northwestern University
- Riley Hospital for Children
- University of Iowa
- Via Christi - St. Francis Regional Medical Center
- Tulane University Health Sciences Center
- Louisiana State University Health Sciences Center
- Central Maine Pulmonary Associates
- University of Michigan
- University of Mississippi Medical Center
- University of Missouri
- St. Louis University
- Children's Lung Specialists
- St. Barnabas Healthcare System
- Albany Medical College
- Long Island Jewish Medical Center
- SUNY Upstate Medical University
- University of North Carolina
- Cincinnati Children's Hospital Medical Center
- University of Pennsylvania Health System
- Children's Hospital of Pittsburgh
- Pediatric Pulmonary Associates, South Carolina
- Baylor Martha Foster Lung Care Center
- Alamo Clinical Research Associates
- University of Utah
- Naval Medical Center
- Pediatric Pulmonary Center/Virginia Commonwealth University
- University of Washington Medical Center
- University of Wisconsin
- Children's Hospital at Westmead
- Westmead Hospital
- Royal Children's Hospital
- Royal Adelaide Hospital
- Alfred Hospital
- Sir Charles Gairdner Hospital
- Princess Margaret Hospital for Children
- Capital Health and the Governors of the University of Alberta
- St. Paul's Hospital
- Queen Elizabeth II Health Sciences Centre
- Brian Lyttle Professional Corporation
- Centre Hospitalier de l'Universite de Montreal (CHUM)
- Auckland District Health Board
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo three times a day (TID)
AZLI 75 mg three times a day (TID)
Arm Description
Outcomes
Primary Outcome Measures
Change in CFQ-R Respiratory Symptoms Scale (RSS) Score
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).
Secondary Outcome Measures
Change in CFQ-R RSS Score
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).
Change in CFQ-R RSS Score
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).
Percent Change in FEV1 (L)
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum
Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.
Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug
Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.
Number of Participants Hospitalized at Least Once Between Day 0 and Day 42
Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00112359
Brief Title
International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
Acronym
AIR-CF1
Official Title
A Phase 3, Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary Pseudomonas Aeruginosa (AIR-CF1)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
April 2007 (Actual)
Study Completion Date
April 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of a 28-day course of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
Detailed Description
CF patients often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called Pseudomonas aeruginosa (PA). Treatment with antibiotics can stop or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and efficacy of AZLI, an investigational formulation of the antibiotic aztreonam and administered TID using the PARI eFlow® electronic nebulizer, in CF patients with PA.
In this study, participant eligibility was assessed at a screening visit 7 to 14 days prior to the baseline visit (Day 0). Those participants who continued to meet eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI TID or placebo TID). Participants returned for clinic visits at Day 14, an end of treatment visit at Day 28, and a follow-up visit 14 days after the last dose of study drug (Day 42).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, Pseudomonas aeruginosa, Pulmonary Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
166 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo three times a day (TID)
Arm Type
Placebo Comparator
Arm Title
AZLI 75 mg three times a day (TID)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AZLI 75 mg three times a day (TID)
Intervention Type
Drug
Intervention Name(s)
Placebo three times a day (TID)
Primary Outcome Measure Information:
Title
Change in CFQ-R Respiratory Symptoms Scale (RSS) Score
Description
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).
Time Frame
Day 0 to Day 28
Secondary Outcome Measure Information:
Title
Change in CFQ-R RSS Score
Description
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).
Time Frame
Day 0 to Day 14
Title
Change in CFQ-R RSS Score
Description
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).
Time Frame
Day 0 to Day 42
Title
Percent Change in FEV1 (L)
Description
Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.
Time Frame
Day 0 to Day 28
Title
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum
Description
Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.
Time Frame
Day 0 to Day 28
Title
Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug
Description
Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.
Time Frame
Day 0 to Day 42
Title
Number of Participants Hospitalized at Least Once Between Day 0 and Day 42
Description
Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.
Time Frame
Day 0 to Day 42
Other Pre-specified Outcome Measures:
Title
Number of Participants With Other Pathogens Present
Description
Sputum samples were collected at all visits for quantitative and qualitative culture for Staphylococcus aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans.
Time Frame
Day 0 to Day 28
Title
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
Description
PA isolates from sputum samples (collected at all visits) were assessed for their susceptibility to aztreonam.
MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism).
MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism).
MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.
Time Frame
Day 0
Title
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL)
Description
PA isolates from sputum samples (collected at all visits) were assessed for their susceptibility to aztreonam.
MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism).
MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism).
MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.
Time Frame
Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
Abnormal nasal potential difference.
PA present in expectorated sputum or throat swab culture at Screening.
FEV1 between (and including) 25% and 75% predicted at Screening.
Negative pregnancy test at Screening.
Ability to perform reproducible pulmonary function tests.
Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
Ability to provide written informed consent.
Exclusion Criteria:
Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.
Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day.
History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years.
History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).
Known local or systemic hypersensitivity to monobactam antibiotics.
Inability to tolerate short-acting bronchodilator use at least three times daily.
Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.
Changes in physiotherapy technique or schedule within 7 days prior to Screening or between Screening and the next visit.
History of lung transplantation.
A chest x-ray indicating abnormal findings at Screening or within the previous 90 days.
Abnormal renal or hepatic function at Screening.
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.
Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Montgomery, MD
Organizational Affiliation
Corus Pharma, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Pediatric Breathing Disorders Clinic
City
Anchorage
State/Province
Alaska
Country
United States
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Miller Children's Hospital
City
Long Beach
State/Province
California
Country
United States
Facility Name
Children's Hospital, Los Angeles
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
Country
United States
Facility Name
Capital Allergy and Respiratory Disease Center
City
Sacramento
State/Province
California
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
University of Florida Health Sciences Center
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
Nemours Children's Clinic, Orlando
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Children's Memorial Hospital / Northwestern University
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
Country
United States
Facility Name
Via Christi - St. Francis Regional Medical Center
City
Wichita
State/Province
Kansas
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Louisiana State University Health Sciences Center
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Central Maine Pulmonary Associates
City
Auburn
State/Province
Maine
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
Country
United States
Facility Name
University of Missouri
City
Columbia
State/Province
Missouri
Country
United States
Facility Name
St. Louis University
City
St. Louis
State/Province
Missouri
Country
United States
Facility Name
Children's Lung Specialists
City
Las Vegas
State/Province
Nevada
Country
United States
Facility Name
St. Barnabas Healthcare System
City
Livingston
State/Province
New Jersey
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
Country
United States
Facility Name
Long Island Jewish Medical Center
City
New Hyde Park
State/Province
New York
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
University of Pennsylvania Health System
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Pediatric Pulmonary Associates, South Carolina
City
Columbia
State/Province
South Carolina
Country
United States
Facility Name
Baylor Martha Foster Lung Care Center
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Alamo Clinical Research Associates
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
Naval Medical Center
City
Portsmouth
State/Province
Virginia
Country
United States
Facility Name
Pediatric Pulmonary Center/Virginia Commonwealth University
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
Country
United States
Facility Name
Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
Country
Australia
Facility Name
Royal Children's Hospital
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Alfred Hospital
City
Prahran
State/Province
Victoria
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
Country
Australia
Facility Name
Princess Margaret Hospital for Children
City
Perth
State/Province
Western Australia
Country
Australia
Facility Name
Capital Health and the Governors of the University of Alberta
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
St. Paul's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Queen Elizabeth II Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
Country
Canada
Facility Name
Brian Lyttle Professional Corporation
City
London
State/Province
Ontario
Country
Canada
Facility Name
Centre Hospitalier de l'Universite de Montreal (CHUM)
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Auckland District Health Board
City
Auckland
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
19420195
Citation
Retsch-Bogart GZ, Quittner AL, Gibson RL, Oermann CM, McCoy KS, Montgomery AB, Cooper PJ. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest. 2009 May;135(5):1223-1232. doi: 10.1378/chest.08-1421.
Results Reference
derived
Learn more about this trial
International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
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