The main objective is to assess target attainment of cefotaxime levels in the critically ill treated with either continuously or intermittently dosed cefotaxime. Secondary objectives are: to develop a predictive mathematical pharmacokinetic (PK)…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Total bound and unbound plasma concentrations of cefotaxime; target attainment
and maintenance at different time intervals based on a predefined target
minimal inhibitory concentration (MIC)
Secondary outcome
Describing cefotaxime PK parameters
Parameters relevant to pharmacokinetic profile of subjects; including ideal
body weight (kgs), actual body weight (kgs), fluid balance (L), creatinine
(mg/mL), creatinine clearance (mL/min), derived from creatinine concentration
in plasma and a 24-hour aliquot of urine, volume of distribution (total drug
dose (mgs) divided by plasma cefotaxime concentration (mg/L)), albumin (mg/mL).
To identify relationships between patient characteristics (e.g. APACHE II
score, serum albumin concentration, kidney function etc.) and cefotaxime levels
that can contribute to optimized dosing in selected patientgroups using
multiple regression.
Background summary
Critically ill patients have other pharmacokinetic/pharmacodynamic profiles
than healthy volunteers. Suboptimal, both under- and overdosing of antibiotics
is an important threat in this patient category. Given the time-dependent
character of beta-lactam antibiotics continuous dosing as opposed to
traditional intermittent dosing is likely to render better target attainment
and maintenance and might improve clinical outcome.
Study objective
The main objective is to assess target attainment of cefotaxime levels in the
critically ill treated with either continuously or intermittently dosed
cefotaxime. Secondary objectives are: to develop a predictive mathematical
pharmacokinetic (PK) model of cefotaxime in the critically ill; to identify
relationships between patient characteristics (e.g. APACHE II score, serum
albumin concentration, kidney function etc.) and cefotaxime levels that can
contribute to optimized dosing in selected patientgroups using multiple
regression.
Study design
Prospective randomized controlled single centre study
Study burden and risks
Patients will be randomized into one of two treatment-arms; one with
intermittent dosing; one with continuous dosing. Both intermittent and
continuous dosing are currently options in our protocol for routine
administration. Blood samples will be drawn on predefined time points after
drug administration through an arterial line placed for routine patient
management. Maximum amount of blood drawn for this study will be 28 mL (8
samples of 2 mL on day 1; 2 samples of 2 mL on day 2 - 4).
Besides the drawing of blood for cefotaxime blood concentration analysis and
anonymous data-collection, in this study patients will not be subjected to any
other intervention.
The risks for subjects included in this study are considered to be minor: small
volume blood samples are drawn from an indwelling catheter.
No benefits are to be expected for human subjects in this experiment. This
study can, however, contribute to optimized dosing of cefotaxime in the
critically ill through enhanced knowledge of pharmacokinetics/pharmacodynamics
in this specific patient category.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
- Adult (>= 18 yrs. of age) patients
- Admitted to intensive care
- Indication for treatment with cefotaxime (as judged by treating physician)
Exclusion criteria
Renal replacement therapy
Contraindications for cefotaxime use
No indication for an arterial line
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 |
|---|---|
| CCMO | NL50809.042.14 |