Cystic FibrosisPhase 3AIR-CF2NCT00104520
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
A Phase 3 study testing AZLI 75 mg two times a day (BID)/three times a day (TID) in people with Cystic Fibrosis, run by Gilead Sciences at 56 sites in United States.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- AZLI 75 mg two times a day (BID)/three times a day (TID)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 211 participants
- Where
- 56 sitesUnited States
- Study dates
- Feb 2005to Sep 2006
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- CF as diagnosed by:
- Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
- Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
- Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
- PA present in expectorated sputum or throat swab culture at Screening.
- Participants must have received three or more courses of TIS within the previous 12 months.
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- Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
- Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
- Ability to perform reproducible pulmonary function tests.
- Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
Who cannot join
- Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
- History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
- History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
- Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
- Known local or systemic hypersensitivity to monobactam antibiotics.
- Inability to tolerate inhalation of a short acting Beta-2 agonist.
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- Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
- Changes in physiotherapy technique or schedule within 7 days before 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 or serum chemistry at Screening (aspartate aminotransferase [AST], alanine aminotransferase [ALT] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
- Positive pregnancy test at Screening.
- Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable birth control.
- 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.
Trial locations and contacts
56 sites in 1 country.
56 sites in 1 country
United States56 sites
Akron Children's Hospital
Akron, Ohio
Albany Medical College
Albany, New York
University of Michigan
Ann Arbor, Michigan
Emory Healthcare
Atlanta, Georgia
Medical College of Georgia
Augusta, Georgia
Children's Hospital, Boston
Boston, Massachusetts
Floating Hospital for Children
Boston, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts
Long Island College Hospital
Brooklyn, New York
Children's Hospital of Buffalo
Buffalo, New York
Medical University of South Carolina
Charleston, South Carolina
Children's Memorial Hospital/Northwestern University
Chicago, Illinois
Pediatric Pulmonary Associates, South Carolina
Columbia, South Carolina
Columbus Children's Hospital, Ohio State University
Columbus, Ohio
Children's Medical Center
Dayton, Ohio
Children's Hospital
Denver, Colorado
Children's Hospital of Michigan/Wayne State University
Detroit, Michigan
University of Florida Health Sciences Center
Gainesville, Florida
Chicago Children's Asthma Respiratory and Exercise Specialists
Glenview, Illinois
Connecticut Children's Medical Center
Hartford, Connecticut
Penn State University Hershey Medical Center
Hershey, Pennsylvania
Baylor College of Medicine
Houston, Texas
Indiana University
Indianapolis, Indiana
Nemours Children's Clinic, Jacksonville
Jacksonville, Florida
University of Kansas Medical Center
Kansas City, Kansas
University of California, San Diego
La Jolla, California
Children's Lung Specialists, Ltd.
Las Vegas, Nevada
University of Arkansas for Medical Sciences
Little Rock, Arkansas
Children's Hospital Los Angeles
Los Angeles, California
Loyola University Medical Center
Maywood, Illinois
University of Miami School of Medicine
Miami, Florida
University of Minnesota
Minneapolis, Minnesota
West Virginia University
Morgantown, West Virginia
Morristown Memorial Hospital
Morristown, New Jersey
Long Island Jewish Medical Center
New Hyde Park, New York
Columbia University Medical Center
New York, New York
North Suburban Pulmonary / Critical Care Consultants
Niles, Illinois
Kaiser Permanente Medical Care Program
Oakland, California
Dr. Santiago Reyes
Oklahoma City, Oklahoma
Children's Hospital, Orange Co.
Orange, California
Nemours Children's Clinic
Orlando, Florida
Stanford University Hospital and Medical Center
Palo Alto, California
Drexel University College of Medicine
Philadelphia, Pennsylvania
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania
Phoenix Children's Hospital
Phoenix, Arizona
Children's Hospital of Pittsburg
Pittsburgh, Pennsylvania
Maine Medical Center
Portland, Maine
Oregon Health & Science University
Portland, Oregon
Rhode Island Hospital
Providence, Rhode Island
Pediatric Pulmonary Center
Richmond, Virginia
UC Davis Medical Center
Sacramento, California
Alamo Clinical Research Associates
San Antonio, Texas
Children's Hospital and Regional Medical Center
Seattle, Washington
Pediatric Pulmonary Associates, Florida
St. Petersburg, Florida
State University of New York Stony Brook
Stony Brook, New York
Children's Hospital of Westchester Medical Center/New York Medical College
Valhalla, New York
About this study
Official title: A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial With Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary P. Aeruginosa Requiring Frequent Antibiotics (AIR-CF2)
The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
Read the detailed description
Patients with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called 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 aztreonam for inhalation solution (AZLI), an investigational formulation of the antibiotic administered using the eFlow® Electronic Nebulizer by PARI GmbH, in CF patients with PA.
In this study, participants were screened for eligibility at Visit 1 (Day -42) and returned to the center for Visit 2 after a 14-day evaluation period. At Visit 2 (Day -28), participants began a 28-day course of open-label Tobramycin Inhalation Solution (TIS). At Visit 3 (Day 0), following completion of the 28-day course of TIS, participants began randomized, blinded treatment with either AZLI twice a day (BID) or three times a day (TID) or placebo BID or TID, and continued treatment for a total of 28 days, with a clinic visit at Day 14 (Visit 4) and at the end of treatment (Visit 5 [Day 28]). Participants returned for visits every 2 weeks for 8 weeks after the end of the blinded treatment (Visits 6 to 9 [Days 42 to 84]).
Two hundred and forty-seven participants were treated in the TIS phase of this study. Two hundred and eleven subjects completed the TIS phase and were treated in the placebo-controlled phase with study drug (AZLI or placebo).
- Conditions
- Cystic Fibrosis
- Being tested
- AZLI 75 mg two times a day (BID)/three times a day (TID), Placebo two times a day (BID)/three times a day (TID)
- Keywords
- Cystic Fibrosis, Pseudomonas aeruginosa, Pulmonary Cystic Fibrosis
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZLI 75 mg two times a day (BID)/three times a day (TID)Drug
Placebo two times a day (BID)/three times a day (TID)Drug
| Study group | Role | What they receive |
|---|---|---|
| Placebo (pooled two times a day [BID]/three times a day [TID]) | Placebo comparator | Not described Receives: Drug: Placebo two times a day (BID)/three times a day (TID) |
| AZLI (pooled two times a day [BID]/three times a day [TID]) | Experimental | Not described Receives: Drug: AZLI 75 mg two times a day (BID)/three times a day (TID) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics
The primary endpoint was time to need for a course of inhaled or IV antipseudomonal antibiotics with documented physician assessment of need for antibiotics. Antipseudomonal Antibiotic need was documented based on the presence of at least one of the following four symptoms predictive of pulmonary exacerbation: decreased exercise tolerance, increased cough, increased sputum / chest congestion, decreased appetite, or other.
Measured: Day 0 to Day 84 (end of study)
Secondary outcomes (4)
Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score
The CFQ-R was administered at Day -28, baseline, Day 14, Day 28, and Day 84 (end of study). The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms).
Measured: Day 0 to Day 28
Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L)
Spirometry was performed at each visit. FEV1 was recorded according to American Thoracic Society (ATS) guidelines.
FEV1(L) is the measurement of the volume of air (expressed in liters) exhaled in 1 second.
The percent change in this parameter from Day 0 to Day 28 was determined for each treatment group.
Measured: Day 0 to Day 28
Number of Hospitalization Days
Details of all hospitalizations, including the dates of admission and discharge, were recorded on the electronic case report form (eCRF).
Measured: Day 0 to Day 84
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.
Measured: Day 0 to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2005 (estimated)
- Study startFeb 2005
- Primary completionSep 2006
- Study completionSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Karen McCoy, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00104520
- Sponsor's protocol ID
- CP-AI-005
- Acronym
- AIR-CF2
- Status last verified
- Sep 2010
- First submitted
- 1 Mar 2005
- Last updated
- 11 Mar 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009 Jun;135(6):1610-1618. doi: 10.1378/chest.08-1190. Epub 2009 May 15.
PubMed 19447923McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8. doi: 10.1164/rccm.200712-1804OC. Epub 2008 Jul 24.
PubMed 18658109
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial With Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary P. Aeruginosa Requiring Frequent Antibiotics (AIR-CF2)
- ClinicalTrials.gov ID
- NCT00104520
- Acronym / sponsor ID
- AIR-CF2 / CP-AI-005
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Pseudomonas aeruginosa, Pulmonary Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 211 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Feb 2005
- Primary completion
- Sep 2006 (actual)
- Study completion
- Sep 2006 (actual)
- First posted
- 2 Mar 2005 (estimated)
- Results
- Posted 11 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
Detailed description
Patients with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called 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 aztreonam for inhalation solution (AZLI), an investigational formulation of the antibiotic administered using the eFlow® Electronic Nebulizer by PARI GmbH, in CF patients with PA.
In this study, participants were screened for eligibility at Visit 1 (Day -42) and returned to the center for Visit 2 after a 14-day evaluation period. At Visit 2 (Day -28), participants began a 28-day course of open-label Tobramycin Inhalation Solution (TIS). At Visit 3 (Day 0), following completion of the 28-day course of TIS, participants began randomized, blinded treatment with either AZLI twice a day (BID) or three times a day (TID) or placebo BID or TID, and continued treatment for a total of 28 days, with a clinic visit at Day 14 (Visit 4) and at the end of treatment (Visit 5 [Day 28]). Participants returned for visits every 2 weeks for 8 weeks after the end of the blinded treatment (Visits 6 to 9 [Days 42 to 84]).
Two hundred and forty-seven participants were treated in the TIS phase of this study. Two hundred and eleven subjects completed the TIS phase and were treated in the placebo-controlled phase with study drug (AZLI or placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (pooled two times a day [BID]/three times a day [TID]) | Placebo comparator | Drug: Placebo two times a day (BID)/three times a day (TID) |
| AZLI (pooled two times a day [BID]/three times a day [TID]) | Experimental | Drug: AZLI 75 mg two times a day (BID)/three times a day (TID) |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- CF as diagnosed by:
- PA present in expectorated sputum or throat swab culture at Screening.
- Participants must have received three or more courses of TIS within the previous 12 months.
- Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
- Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
Key exclusion criteria (14 listed)
- Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
- History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
- History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
- Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
- Known local or systemic hypersensitivity to monobactam antibiotics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZLI 75 mg two times a day (BID)/three times a day (TID) | Drug | AZLI (pooled two times a day [BID]/three times a day [TID]) |
| Placebo two times a day (BID)/three times a day (TID) | Drug | Placebo (pooled two times a day [BID]/three times a day [TID]) |
Primary outcome
Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics
Time frame: Day 0 to Day 84 (end of study)
The primary endpoint was time to need for a course of inhaled or IV antipseudomonal antibiotics with documented physician assessment of need for antibiotics. Antipseudomonal Antibiotic need was documented based on the presence of at least one of the following four symptoms predictive of pulmonary exacerbation: decreased exercise tolerance, increased cough, increased sputum / chest congestion, decreased appetite, or other.
4 secondary outcomes
Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score
Time frame: Day 0 to Day 28
Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L)
Time frame: Day 0 to Day 28
Number of Hospitalization Days
Time frame: Day 0 to Day 84
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum
Time frame: Day 0 to Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19447923Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009 Jun;135(6):1610-1618. doi: 10.1378/chest.08-1190. Epub 2009 May 15.
- Derived from this study: PubMed 18658109McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8. doi: 10.1164/rccm.200712-1804OC. Epub 2008 Jul 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen McCoy, MD principal investigator
Nationwide Children's Hospital
56 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZLI 75 mg two times a day (BID)/three times a day (TID) in people with Cystic Fibrosis, run by Gilead Sciences at 56 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics (time frame: Day 0 to Day 84 (end of study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00104520, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2011.