Dose individualization of beta-lactam and fluoroquinolone antibiotics in intensive care unit patients

Dose IndividualizAtion of Beta-lactam and fluOroquinoLone AntiBiotics in ICU patients: to TDM or not to TDM and the effects on Outcome (DIABOLO-study) - DIABOLO

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-004677-14-NL

Enrollment

250

Registered

2018-03-06

Start date

2018-03-09

Completion date

Unknown

Last updated

2018-03-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ICU patients with infection

Interventions

Trade Name: Cefotaxim 500mg, 1000mg Pharmaceutical Form: Powder for solution for injection Trade Name: Ceftazidim 500mg, 1000mg, 2000mg Pharmaceutical Form: Powder for solution for injection Trade N

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: All patients admitted to the ICU and given standard of care intravenous therapy of either one or both of the target antibiotic classes are included. Antibiotic initiation based on clinical suspicion of infection and/or cultured pathogens susceptible to the target drugs, initial dosage prescription, and duration of therapy are at the discretion of the attending physician. In order to be eligible to participate in this study, a subject must also meet all of the following criteria: •=18 years of age •Receiving intravenous antibiotic therapy of the target drugs •Treatment should be aimed for at least 2 days. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150

Exclusion criteria

Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: •Pregnancy •Patient already enrolled in this trial •Antibiotic cessation before sampling •Medium care and burn wound patients admitted to the ICU •Patients receiving cefotaxime as prophylaxis only within the context of Selective Digestive tract Decontamination (SDD)

Design outcomes

Primary

Measure	Time frame
Main Objective: The aim of this trial is to evaluate a new early dosage adjustment strategy (TDM) of beta-lactam and fluoroquinolones in adult ICU patients to achieve the adequate pharmacodynamic targets (PDT), compared to the usual treatment strategy.;Secondary Objective: Secondary aims are clinical outcome, the impact on antimicrobial resistance, and cost-effectiveness analyses between the TDM and non-TDM group.;Primary end point(s): Attainment of drug levels will be calculated using the PDT. PDT indices are calculated for each individual patient. The treatment drug MICECOFF and the free (unbound = ƒ) drug exposure value are used to calculate the following PK/PD indices: •Beta-lactam: %ƒT>MICECOFF (including % of patients with 100%ƒT>MICECOFF in both groups). This means that patients need an unbound beta-lactam serum concentration of 100% above the MIC during a dosing interval. •Fluoroquinolone: ƒAUC/MICECOFF (including % of patients with ƒAUC/MICECOFF=100 in both groups) This means that patients need an unbound area under the curve concentration equals or above 100/MIC ratio during the dosing interval. The area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. ;Timepoint(s) of evaluation of this end point: 24-months	—

Measure

Time frame

Main Objective: The aim of this trial is to evaluate a new early dosage adjustment strategy (TDM) of beta-lactam and fluoroquinolones in adult ICU patients to achieve the adequate pharmacodynamic targets (PDT), compared to the usual treatment strategy.;Secondary Objective: Secondary aims are clinical outcome, the impact on antimicrobial resistance, and cost-effectiveness analyses between the TDM and non-TDM group.;Primary end point(s): Attainment of drug levels will be calculated using the PDT. PDT indices are calculated for each individual patient. The treatment drug MICECOFF and the free (unbound = ƒ) drug exposure value are used to calculate the following PK/PD indices: •Beta-lactam: %ƒT>MICECOFF (including % of patients with 100%ƒT>MICECOFF in both groups). This means that patients need an unbound beta-lactam serum concentration of 100% above the MIC during a dosing interval. •Fluoroquinolone: ƒAUC/MICECOFF (including % of patients with ƒAUC/MICECOFF=100 in both groups) This means that patients need an unbound area under the curve concentration equals or above 100/MIC ratio during the dosing interval. The area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. ;Timepoint(s) of evaluation of this end point: 24-months

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Secondary

Measure	Time frame
Secondary end point(s): The secondary aims are to compare TDM-tailored group with the usual treatment strategy with respect to 1) the proportion of subjects with serum concentration within the concentration targets, and 2) the clinical (e.g. in terms of fever), biological (e.g. in terms of CRP) and bacteriological (e.g. in terms of blood culture) efficacy of this early dosage adjustment strategy of beta-lactam and fluoroquinolone antibiotics. Furthermore, the impact on antimicrobial resistance (AMR) will be measured by taking samples from the presumptive infection, using culture techniques and quantitative PCR (qPCR). This technique was recently described for carbapenemases and in our own research group for ESBLs. Subsequently, the results will be plotted as a function of ƒT>MIC and ƒAUC/MIC to determine specific patterns. The advantage of this approach is that even if there is no significant difference between the groups, it may still provide a distinctive pattern over the whole study group. ;Timepoint(s) of evaluation of this end point: 24-months	—

Measure

Time frame

Secondary end point(s): The secondary aims are to compare TDM-tailored group with the usual treatment strategy with respect to 1) the proportion of subjects with serum concentration within the concentration targets, and 2) the clinical (e.g. in terms of fever), biological (e.g. in terms of CRP) and bacteriological (e.g. in terms of blood culture) efficacy of this early dosage adjustment strategy of beta-lactam and fluoroquinolone antibiotics. Furthermore, the impact on antimicrobial resistance (AMR) will be measured by taking samples from the presumptive infection, using culture techniques and quantitative PCR (qPCR). This technique was recently described for carbapenemases and in our own research group for ESBLs. Subsequently, the results will be plotted as a function of ƒT>MIC and ƒAUC/MIC to determine specific patterns. The advantage of this approach is that even if there is no significant difference between the groups, it may still provide a distinctive pattern over the whole study group. ;Timepoint(s) of evaluation of this end point: 24-months

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Countries

Netherlands

Contacts

Public ContactHospital Pharmacist

Erasmus MC

b.koch@erassmusmc.nl+310107033202

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026