Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (AIR-CF2)
Drug: 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)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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)|
- Time to Need for Inhaled or Intravenous (IV) Antipseudomonal Antibiotics [ Time Frame: Day 0 to Day 84 (end of study) ] [ Designated as safety issue: No ]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.
- Change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]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).
- Percent Change in Forced Expiratory Volume in 1 Second (FEV1) (L) [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]
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.
- Number of Hospitalization Days [ Time Frame: Day 0 to Day 84 ] [ Designated as safety issue: No ]Details of all hospitalizations, including the dates of admission and discharge, were recorded on the electronic case report form (eCRF).
- Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum [ Time Frame: Day 0 to Day 28 ] [ Designated as safety issue: No ]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.
|Study Start Date:||February 2005|
|Study Completion Date:||September 2006|
|Primary Completion Date:||September 2006 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo (pooled two times a day [BID]/three times a day [TID])||Drug: Placebo two times a day (BID)/three times a day (TID)|
|Experimental: AZLI (pooled two times a day [BID]/three times a day [TID])||Drug: AZLI 75 mg two times a day (BID)/three times a day (TID)|
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00104520
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|Principal Investigator:||Karen McCoy, MD||Nationwide Children's Hospital|