Main objective: To compare the renal elimination rate constant in CF patients receiving a daily intravenous dose of tobramycin in the morning against patients receiving a daily intravenous dose of tobramycin in the evening. Secondary objective: To…
ID
Source
Brief title
Condition
- Respiratory disorders congenital
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end point will be a significant or non-significant difference in
the elimination rate constant (Kel) between CF patients receiving a daily
intravenous dose of tobramycin in the morning and CF patients receiving a daily
intravenous dose of tobramycin in the evening.
Secondary outcome
biochemical signs of nephrotoxicity (NAG and creatinine) in patients who
receive their dose of tobramycin in the morning against patients who receive
their dose of tobramycin in the evening.
Background summary
Aminoglycosides are a cornerstone for the treatment of cystic fibrosis
patients, who have a chronic pulmonary infection with Pseudomonas aeruginosa1.
This class of antibiotics is very effective against infections with Pseudomonas
aeruginosa, which is the most important pathogen in cystic fibrosis. Repeated
or extended dosing of aminoglycosides may cause damage to the proximal tubuli,
resulting in renal impairment. Renal impairment affects up to 40 % of adult CF
patients, measured after estimation using an appropriate formula. The true
number is probably even greater. Life expectancy of CF patients is extending as
a result of better treatment. This makes toxicity caused by intravenous
aminoglycosides now more relevant than for instance 30 years ago. The TOPIC
study has shown that once-daily dosing of aminoglycosides is at least as
effective and may be less toxic compared to multiple daily dosing8. A recent
post-hoc analysis of the TOPIC study data revealed that this difference was
probably caused by the fact that 53 out of the 71 patients received their
active dose between 16:00 and 20:00 h20. This may be the result of a circadian
rhythm in drug clearance. It is our hypothesis the circadian rhythm (and
mobility) influences the renal elimination rate of tobramycin in CF patients.
Study objective
Main objective: To compare the renal elimination rate constant in CF patients
receiving a daily intravenous dose of tobramycin in the morning against
patients receiving a daily intravenous dose of tobramycin in the evening.
Secondary objective: To compare biochemical signs of nephrotoxicity in patients
who receive their dose of tobramycin in the morning against patients who
receive their dose of tobramycin in the evening.
Study design
Open randomized trial
Intervention
Subjects will be randomized to receive their daily dose of tobramycin in the
morning or in the evening. At present tobramycin is administered randomly
throughout the day.
Study burden and risks
The only extra burden associated with participation is three 24-hour urine
collections. There are no extra risks associated with participation other than
the risks associated with standard treatment.
Bleulandweg 10
2803 HH Gouda
NL
Bleulandweg 10
2803 HH Gouda
NL
Listed location countries
Age
Inclusion criteria
- Age: * 18 years
- a diagnosis of cystic fibrosis (ie, sweat chloride *60 mmol/L or a genotype associated with cystic fibrosis)
- chronic infection with Pseudomonas aeruginosa with the most recently isolated organism showing sensitivity to tobramycin.
- Pulmonary exacerbation as defined by Fuchs and colleagues.
Exclusion criteria
- use of nephrotoxic drugs (NSAID*s, furosemide, vancomycin)
- allergy for aminoglycosides
- granulocytopenia (<1,0 x 109/L)
- pregnancy
- calculated GFR < 40 ml/min
- pre-existing hearing impairment ( * 20 dB hearing level at any two frequencies between 2kHz and 8 kHz on the standard audiogram)
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-005110-41-NL |
| CCMO | NL24568.098.08 |