Primary objective: To investigate whether pharmacokinetics of the recommended dose of inhaled tobramycin, defined as serum tobramycin Area Under the Curve (AUC0-24hr), with the I-neb (75 mg) is equivalent to the PariLCPlus (300 mg) nebuliser in…
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Primary endpoint: systemic bioavailability of inhaled tobramycin, defined as
serum tobramycin AUC0-24hr.
Secondary outcome
Secondary endpoints include: change in hearing function, renal toxicity, serum
tobramycin peak and trough levels, change in lung function (difference in
FEV1), result sputum/throat swab, compliance rate, patient satisfaction,
quality of life (CFQ) and age-related differences in serum tobramycin
AUC0-24hr.
Background summary
A study is proposed to investigate whether inhalation of tobramycin with the
I-neb nebuliser is equivalent to inhalation with the conventional nebuliser,
PariLCPlus, in children with cystic fibrosis (CF).
Inhaled tobramycin has been shown to be effective in eradication of early
Pseudomonas Aeroginosa (PA) infection in children with CF.1;2 Tobramycin also
improves lung function and outcome in children who are chronically colonised
with PA.3 In both groups quality of inhalation and treatment adherence are of
utmost importance for efficacy. However, nebulisation is a daily time-consuming
nuisance for children with CF. Therefore, compliance and quality of inhalation
are often low, which impairs effective treatment. A rapid nebuliser would
improve quality of life. With the highly efficient I-neb nebuliser nebulisation
time is reduced to 4 minutes compared to 25 minutes with the conventional
PariLCPlus nebuliser.
The I-neb is already widely used in adults and increasingly in children.
However, it has not been tested in children yet and little is known about
pharmacokinetics and safety of the medications used by this population. Dose
recommendations are based on in vitro tests and studies in adults. The same
doses are used for children and adults. Theoretically, the efficient I-neb
design could lead to higher serum levels and potential toxic effects. Before
the I-neb can be implemented on a routine basis in paediatric CF care, one
needs to know whether it is safe to use. Therefore we would like to investigate
whether inhalation of the recommended dose of tobramycin - when using the I-neb
- is safe in children. If inhalation with the I-neb is equivalent to inhalation
with the PariLCPlus and no toxicity is shown, the I-neb can be used safely.
However, if toxicity is shown, dose adjustments need to be made to prevent
long-term damage.
Study objective
Primary objective: To investigate whether pharmacokinetics of the recommended
dose of inhaled tobramycin, defined as serum tobramycin Area Under the Curve
(AUC0-24hr), with the I-neb (75 mg) is equivalent to the PariLCPlus (300 mg)
nebuliser in children with CF aged 6-18 years.
Secondary objectives: 1) To assess safety of I-neb tobramycin inhalation
therapy, 2) to compare pharmacokinetics of I-neb tobramycin inhalation in
children with CF aged 6-11 years with children aged 12-18 years and 3) to
assess patient compliance and satisfaction with the I-neb nebuliser.
Study design
Open label, multi centre, randomised controlled cross-over trial.
Intervention
24 patients will be inhaling tobramycin at home for 28 days using the I-neb.
Study burden and risks
Target population of this study are children, because limited information is
available on inhalation with the I-neb in this population. However, especially
for children with CF a more rapid and convenient nebuliser may improve quality
of life.
Children participating in this study will be treated at home and will visit the
hospital for two study visits. During each visit several tests will be
performed, including spirometry, audiometry, blood/urine sampling. The risks
associated with participation are small. Tobramycin (BRAMITOB®) is a registered
drug since 2007 for treatment of chronic PA lung infection in CF-patients 6
years and older. Inhalation of tobramycin in children with CF is proven to be
effective and safe in multiple studies. The I-neb is already used in the UK on
a large scale for this purpose, although there are limited data available.4
Serious and life threatening side effects have not been described. The I-neb
design may lead to a higher systemic exposure of tobramycin in children. Due to
the short period of exposure all potential toxic effects are expected to be
small and presumably reversible.
Dr. Molewaterplein (kamer Sp 3456) 60
Rotterdam 3015 GJ
NL
Dr. Molewaterplein (kamer Sp 3456) 60
Rotterdam 3015 GJ
NL
Listed location countries
Age
Inclusion criteria
- Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
- Either: early PA infection or colonization with PA requiring eradication with inhaled tobramycin, or: chronic PA colonization requiring maintenance therapy with inhaled tobramycin;
- Age 6-18 years;
- Ability to breathe through a mouthpiece and to use both types of inhalers;
- Ability to perform lung function tests;
- Written informed consent (parents; >12 years: child and parents).
Exclusion criteria
- Severe acute exacerbation of pulmonary infection needing intravenous treatment;
- Known impaired kidney function (estimated creatinine clearance < 60 ml/min);
- 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2012-002503-17-NL |
CCMO | NL40970.078.12 |