Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.

Does Continuous Cefotaxime Administration Improve Time to Attainment and Maintenance of Target Drug Levels in Critically Ill Patients?

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.

Study Overview

• Status: Completed
• Conditions: Critically Ill
• Intervention / Treatment: Drug: 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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intermittent cefotaxime; Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days	Drug: Cefotaxime; To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.; Other Names: Claforan
EXPERIMENTAL: Continuous 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 .	Drug: Cefotaxime; To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.; Other Names: Claforan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cefotaxim serum concentrations	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.	40 min, 1 hour, 2, 4, 8, 12 and 24 hours; 36h; 48 h; 60h; 72h; 84h and 96h post administration

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Jan G Zijlstra, MD, PhD, department of critical care, UMCG

Publications and helpful links

General Publications

• Aardema H, Bult W, van Hateren K, Dieperink W, Touw DJ, Alffenaar JC, Zijlstra JG. Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations. J Antimicrob Chemother. 2020 Feb 1;75(2):441-448. doi: 10.1093/jac/dkz463.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: September 22, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (ESTIMATE): September 25, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Anti-Infective Agents; Anti-Bacterial Agents; Cefotaxime; Cefoxitin
• Other Study ID Numbers: 2014/468