Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.

Phase 4

Completed

• Conditions: Critically Ill
• Interventions: Drug: Cefotaxime

• Registration Number: NCT02560207
• Lead Sponsor: University Medical Center Groningen

Brief Summary

This study evaluates target attainment after either intermittent intravenous bolus or intravenous continuous infusion of cefotaxime in critically ill patients. Critically ill patients will be randomized to intermittent infusion or continuous infusion of cefotaxime.

Detailed Description

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 Timeline

• Study First Submitted: 2015-09-22
• Study First Submitted QC: 2015-09-24
• Study First Posted: 2015-09-25
• Study Start: 2015-11
• Primary Completion: 2016-06
• Study Completion: 2016-09
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-26
• Last Update Posted: 2016-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Admitted to intensive care
• Able to give informed consent by themselves or informed consent can be obtained via next of kin
• Indication for treatment with cefotaxime (as judged by treating physician) in the context of our standard treatment protocol of Selective decontamination of the digestive tract (SDD).

Exclusion Criteria

• Renal replacement therapy
• Contra-indication for cefotaxime, including known or suspected allergy to cefotaxime
• No indication for an arterial line; an arterial line will not be placed solely for the purpose of this study; thus, only patients with an indication for an arterial line outside this protocol are eligible.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intermittent cefotaxime	Cefotaxime	Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days
Continuous cefotaxime	Cefotaxime	After a 1 gram (1000 mg) Cefotaxime loading dose, Cefotaxime 4 gram (4000 mg) is to be administered as a continuous infusion in 24h for 4 days .

Primary Outcome Measures

Name	Time	Method
Cefotaxim serum concentrations	40 min, 1 hour, 2, 4, 8, 12 and 24 hours; 36h; 48 h; 60h; 72h; 84h and 96h post administration	Cefotaxime serum concentrations, total and unbound, will be determined. The Pharmacokinetic/Pharmacodynamic (PK/PD) target of total serum concentration of 4 times above minimal inhibitory concentration (MIC) ascertains that the unbound drug serum concentration will be above the MIC value of 1 mg/mL, which is determined to be the minimum target.

Secondary Outcome Measures

Name	Time	Method
Area under the curve of cefotaxim	0-96h post administration	Based on the data from the primary outcome measure a pharmacokinetic model for ICU patients will be developed.

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands