Cystic Fibrosis and chronic infection with Pseudomonas aeuroginosa MedDRA version: 22.1 Level: LLT Classification code 10057582 Term: Lung infection pseudomonal System Organ Class: 100000004862
Conditions
Interventions
Trade Name: BRAMITOB - 300 MG/4 ML SOLUZIONE DA NEBULIZZARE 56 CONTENITORI MONODOSE 4 ML
Product Name: Bramitob
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: TOBRAMICINA
CAS Number: 3
Sponsors
ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM
Eligibility
Sex/Gender
All
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). Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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; •Use of Tobramycin Inhalation Powder as part of the maintenance therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the change in small airways obstruction (FEF75%) in patients with CF when inhaling one ampule of 300 mg of inhaled tobramycin with the Akita® compared to standard of treatment (twice daily nebulization of one ampule of 300 mg using standard nebulizer equipment);Secondary Objective: 1. To compare changes in lung function parameters (FEV1, FVC, FEF25-75%, MMEF25-75) and LCI. 2. To compare changes in bacterial CFUs of Pseudomonas aeruginosa in sputum between both treatment arms. 3. To compare the effect on ‘trapped air’ between both treatment arms as depicted by spirometer controlled expiratory chest Magnetic Resonance Imaging (MRI). 4. To assess safety of Akita® tobramycin inhalation therapy in CF-patients by monitoring trough levels of tobramycine, ototoxicity and nephrotoxicity. ;Primary end point(s): change in FEF75 (Z-score and L/s) after 4 weeks of targeted treatment.;Timepoint(s) of evaluation of this end point: Every study visit. Patients will be included for 3 months and study visit are planned at the start and end of the first andthird month. 4 study visits in total | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •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, 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. ;Timepoint(s) of evaluation of this end point: 4 weeks; 4 weeks; 4 weeks; 4 weeks; study visit 2 and 4 | — |
Countries
Italy, Netherlands
Contacts
Public ContactPrincipal Investigator Netheralnds
Erasmus MC- Sophia Children's Hospital
Outcome results
None listed