Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis
Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis
This study assessed time to recurrence of infection with Pseudomonas aeruginosa following
 treatment of the initial infection with tobramycin nebuliser solution. The safety profile of
 the initial tobramycin treatment was assessed during the first 3 months of the study and
 patients were followed until the end of the study, month 27.
This was a multi-center, open-label, two-arm, randomized study. All patients diagnosed with
 CF and who fulfilled the criteria for early infection with P. aeruginosa initially received
 tobramycin 300 mg twice a day for 28 days. At the end of the 28-day treatment period,
 patients who met the inclusion criteria and none of the additional exclusion criteria were
 randomized in a 1:1 ratio to either receive an additional 28 days of treatment with
 tobramycin 300 mg twice a day (56-day group) or to stop study medication (28-day group).

 All randomized patients had regular study visits until a positive P. aeruginosa sample was
 obtained. Once P. aeruginosa had recurred, the patient entered a follow-up phase where
 minimal information was collected for 27 months. During the follow-up phase, patients were
 treated according to their physicians' discretion.

 Patients who started treatment with tobramycin but were not randomized (i.e. due to a
 positive antibody test) and followed up during routine clinic visits. They were allowed to
 continue their 28-day treatment period and afterwards be treated according to their
 physicians' discretion.
Inclusion criteria:

 -  Male or female patients ≥ 6 months old

 -  Diagnosis of cystic fibrosis (CF) based upon the following historical criteria
 performed prior to study participation:

 1. confirmed sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis (at
 least 2 tests), OR

 2. genotype with two identifiable mutations consistent with CF.

 -  First or early lower respiratory tract infection with Pseudomonas (P.) aeruginosa
 documented by either of the following:

 1. first infection defined by the first P. aeruginosa isolated from sputum or deep
 throat cough swab culture, OR

 2. P. aeruginosa from sputum or deep throat cough swab culture following at least 1
 year of negative cultures (documented with at least 4 negative cultures during
 this year and no positive cultures) and no anti-pseudomonal treatment during this
 1-year period, OR

 3. P. aeruginosa from sputum or deep throat cough swab culture following at least 2
 years of negative cultures (documented with at least 2 negative cultures per year
 and no positive cultures) and no anti-pseudomonal treatment during this 2-year
 period.

 -  Written informed consent by the patient and/or parent/legal guardian according to
 local country regulations.

 Exclusion criteria:

 -  History of aminoglycoside hypersensitivity or adverse reaction to inhaled
 aminoglycoside.

 -  Signs and symptoms of acute pulmonary disease, eg, pneumonia, pneumothorax.

 -  Administration of any investigational drug within 30 days prior to enrollment.

 -  Administration of loop diuretics within 7 days prior to study drug administration.

 -  Personal/family history of abnormal hearing, other than typical hearing loss
 associated with the aging process.

 -  Abnormal result from an audiology testing (defined as either a unilateral pure-tone
 audiometry test showing a threshold elevation > 20 decibels [dB] at any frequency
 across the frequency range 0.25-8 kHz or the absence of emission at the evoked
 otoacoustic emission test).

 -  Positive urine pregnancy test at Day 1 (Baseline) for all female patients who have
 reached menarche.

 -  Use of macrolide antibiotics as a maintenance therapy for 12 or more days during the
 28 days prior to Baseline.

 -  Antibody titers ≥ 1000 for any of the 3 P. aeruginosa exoenzymes: Exotoxin A, alkaline
 protease, or elastase (status to be determined between Baseline and Day 28).