Cystic Fibrosis Tobramycin
Conditions
Interventions
Patients will nebulize tobramycin during 2 months in a cross-over setting: 1 month nebulization with the Akita nebulizer (once daily 300 mg tobramycin instead of twice daily 150 mg) and 1 month the re
Sponsors
Erasmus Medical Center - Sophia Children's Hospital
Eligibility
Inclusion criteria
Inclusion criteria: • Age ≥ 12 years • Clinical diagnosis of CF and a positive sweat test or two CF-related mutations; • Chronic Pa colonization requiring maintenance therapy with inhaled tobramycin, defined according to the Leeds criteria (>50% Pa positive airway cultures over last 12 months) 22; • Small airways obstruction present on spirometry (defined as follows: dissociation between FVC and FEF75 values (i.e. FEF75 at least 20% (absolute percent predicted) less than FVC); • Ability to breathe through a mouthpiece and to use the inhaler; • Ability to perform lung function tests; • Written informed consent (12-18 years: child and parents; ≥ 18 years: patient).
Exclusion criteria
Exclusion criteria: • Severe acute exacerbation of pulmonary infection (needing intravenous treatment) within one month prior to start or during the study; • Known impaired kidney function (estimated creatinine clearance < 60 ml/min); • Known aminoglycoside hypersensitivity; • Start of nephrotoxic or ototoxic drugs, e.g. aminoglycosides, within 1 month prior to start or during the study; • Therapy (e.g. furosemide) or disease which may complicate evaluation of the study protocol, as judged by the investigator; • Participation in another drug-investigating clinical study at the start or within 1 month prior to the start; • Inability to follow instructions of the investigator. • Use of Tobramycin Inhalation Powder as part of the maintenance therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| change in FEF75 (Z-score and L/s) after 4 weeks of targeted treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| • Change in FEV1, FVC, FEF25, FEF50, MMEF25-75 (Z-scores and absolute values); • Change in Lung Clearance Index (LCI) measurements as assessed by multiple breath washout; • Change in Pa bacterial CFUs (defined as the log10 value for the number of Pa CFUs per millilitre of sputum, either expectorated or collected by suction of the oropharynx); • Change in percentage of trapped air on MRI (% of total lung volume); • Change in FEV1 before and after nebulisation (safety parameter); • Systemic bioavailability of inhaled tobramycin, defined by trough level; • Change in creatinine and blood urea nitrogen (BUN) values as measure of early renal toxicity; • Change in hearing function (measured by HFPTA); • Compliance rate; • Patient satisfaction (use of device); • Cystic Fibrosis questionnaire-revised (CFQ-R): respiratory symptoms scale scores and treatment burden scale scores. | — |
Contacts
Public ContactH.M. Janssens
Dr. Molewaterplein (kamer Sp 3456) 60,
Outcome results
None listed