Efficacy and Safety of 28 or 56 Day Treatment for Pseudomonas Aeruginosa in Children With Cystic Fibrosis
Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis
Intervention: Tobramycin solution for inhalation 300 mg (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Novartis Official(s) and/or principal investigator(s): Felix Ratjen, Principal Investigator, Affiliation: Royal Victoria Infirmary
Summary
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.
Clinical Details
Official title: The Microbiologic Efficacy and Safety of Two Treatment Regimens of Inhaled Tobramycin Nebuliser Solution (TNS) for the Treatment of Early Onset Pseudomonas Aeruginosa Lower Respiratory Tract Infection in Subjects With Cystic Fibrosis
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Time to Recurrence of Pseudomonas (P.) Aeruginosa (Any Genotype) in Sputum or Deep Throat Cough Swab
Secondary outcome: Percentage of Patients With Pseudomonas (P.) Aeruginosa Eradicated From Deep Throat Cough Swab or SputumTime to Recurrence of Pseudomonas (P.) Aeruginosa (New or Same Genotype) in Sputum or Deep Throat Cough Swab Based on Confirmatory Assessment by the Central Laboratory Percentage of Patients With Pseudomonas (P.) Aeruginosa Having an Increased, Decreased, or Unchanged Tobramycin Minimum Inhibitory Concentration (MIC) Value at the Final Visit Compared to Baseline Number of Participants Hospitalized for Pulmonary Exacerbations
Detailed 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.
Eligibility
Minimum age: 6 Months.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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).
Locations and Contacts
Additional Information
Starting date: November 2003
Last updated: July 29, 2011
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