No registrations found.
ID
Source
Brief title
Health condition
cystic fibrosis
cystische fibrose
kidney damage
nierschade
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare the renal clearance of tobramycin in CF patients receiving a daily intravenous dose in the morning against patients receiving a daily intravenous dose of tobramycin in the evening.
Secondary outcome
To compare biochemical parameters of kidney function in patients who receive a dose of tobramycin in the morning against patients who receive a dose of tobramycin in the evening.
Background summary
Rationale:
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 dosing. 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 h. 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.
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.
Study population:
Adult cystic fibrosis patients, admitted to hospital for treatment of pulmonary exacerbation.
Intervention:
Subjects will be randomized to receive their daily dose of tobramycin in the morning or in the evening.
Main study parameters/endpoints:
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.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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.
Study objective
The circadian rhythm influences the renal clearance of tobramycin in cystic fibrosis patients.
Study design
Renal clearance of tobramycin and biochemical paramaters of kidney function will be evaluated on day 1, 7 and day 14 of tobramycin therapy.
Intervention
Subjects will be randomized to receive their daily dose of tobramycin in the morning or in the evening.
Erik Maarseveen, van
University Medical Center Utrecht
Department of clinical pharmacy
Division Laboratory and Pharmacy
D00.218
Utrecht 3508 GA
The Netherlands
+31 (0)88 7551212
e.m.vanmaarseveen@umcutrecht.nl
Erik Maarseveen, van
University Medical Center Utrecht
Department of clinical pharmacy
Division Laboratory and Pharmacy
D00.218
Utrecht 3508 GA
The Netherlands
+31 (0)88 7551212
e.m.vanmaarseveen@umcutrecht.nl
Inclusion criteria
1. Age: ≥ 18 years;
2. A diagnosis of cystic fibrosis (ie, sweat chloride ≥ 60 mmol/L or a genotype associated with cystic fibrosis);
3. Chronic infection with Pseudomonas aeruginosa with the most recently isolated organism showing sensitivity to tobramycin;
4. Pulmonary exacerbation as defined by Fuchs and colleagues.
Exclusion criteria
1. Use of nephrotoxic drugs (NSAID´s, furosemide, vancomycin);
2. Allergy for aminoglycosides;
3. Granulocytopenia (<1,0 x 109/L);
4. Pregnancy;
5. Calculated GFR < 40 ml/min;
6. Pre-existing hearing impairment (≥ 20 dB hearing level at any two frequencies between 2kHz and 8 kHz on the standard audiogram).
Design
Recruitment
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 |
|---|---|
| NTR-new | NL3165 |
| NTR-old | NTR3309 |
| Other | : 08-107 |