Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.
Primary Purpose
Critically Ill
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Cefotaxime
Sponsored by
About this trial
This is an interventional basic science trial for Critically Ill
Eligibility Criteria
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.
Sites / Locations
- University Medical Center Groningen
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Intermittent cefotaxime
Continuous cefotaxime
Arm Description
Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days
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 .
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Area under the curve of cefotaxim
Based on the data from the primary outcome measure a pharmacokinetic model for ICU patients will be developed.
Full Information
NCT ID
NCT02560207
First Posted
September 22, 2015
Last Updated
October 26, 2016
Sponsor
University Medical Center Groningen
1. Study Identification
Unique Protocol Identification Number
NCT02560207
Brief Title
Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.
Official Title
Does Continuous Cefotaxime Administration Improve Time to Attainment and Maintenance of Target Drug Levels in Critically Ill Patients?
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critically Ill
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intermittent cefotaxime
Arm Type
Active Comparator
Arm Description
Cefotaxime 1 gram (1000 mg) is to be administered 4 times daily for 4 days
Arm Title
Continuous cefotaxime
Arm Type
Experimental
Arm Description
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 .
Intervention Type
Drug
Intervention Name(s)
Cefotaxime
Other Intervention Name(s)
Claforan
Intervention Description
To assess the influence of administration route on target attainment cefotaxime is administered via two IV routes.
Primary Outcome Measure Information:
Title
Cefotaxim serum concentrations
Description
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.
Time Frame
40 min, 1 hour, 2, 4, 8, 12 and 24 hours; 36h; 48 h; 60h; 72h; 84h and 96h post administration
Secondary Outcome Measure Information:
Title
Area under the curve of cefotaxim
Description
Based on the data from the primary outcome measure a pharmacokinetic model for ICU patients will be developed.
Time Frame
0-96h post administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan G Zijlstra, MD, PhD
Organizational Affiliation
Department of Critical Care, UMCG
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
31697336
Citation
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.
Results Reference
derived
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Randomized Trial of Continuous Versus Intermittent Cefotaxime Infusion on ICU.
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