Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis (ELITE)

Novartis

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: Tobramycin solution for inhalation 300 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00391976

CTBM100B2301

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 123 patients

Sex: All

Ages: 6+ months old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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123 participants in 2 patient groups

Tobramycin 300 mg for 28 days

Experimental group

Description:

Patients inhaled tobramycin 300 mg bis in die (bid, twice a day) for 28 days using the PARI LC PLUS™ jet nebulizer and a suitable compressor. The 2 daily doses were taken approximately 12 hours apart and no less than 6 hours apart.

Treatment:

Drug: Tobramycin solution for inhalation 300 mg

Tobramycin 300 mg for 56 days

Experimental group

Description:

Patients inhaled tobramycin 300 mg bis in die (bid, twice a day) for 56 days using the PARI LC PLUS™ jet nebulizer and a suitable compressor. The 2 daily doses were taken approximately 12 hours apart and no less than 6 hours apart.

Treatment:

Drug: Tobramycin solution for inhalation 300 mg