Target Attainment of Cefuroxim

NCT05200975 | Unknown DMC

• 1 other identifier: NL78342.029.21
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

SUMMARY Rationale: Optimal antibiotic dosing in patients with bacterial infections is of high importance. Underdosing can lead to treatment failure and can promote emergence of antimicrobial resistance, while overdosing may lead to (harmful) side effects. The antibiotic cefuroxime is a second-generation cephalosporin and is frequently used in hospitalized patients. Cefuroxime exhibits, like other cephalosporins, time-dependent killing. The pharmacodynamic target can therefore be best described as the percentage of the dosing interval that the serum concentration remains above the minimum inhibitory concentration (MIC) of the bacteria (T\>MIC). Attaining the pharmacokinetic-pharmacodynamic (PK-PD) target of 50%T\>MIC is associated with antimicrobial therapeutic efficacy of cefuroxime. Because cefuroxime is almost exclusively excreted through the kidneys, dose reduction of cefuroxime for patients with renal impairment (eGFR\<30ml/min/1.73m2) is standard of care. No prospective evidence exists that currently guideline-recommended cefuroxime dosing regimens result in at least 50%T\>MIC in adult patients on general wards, especially not in patients with renal impairment receiving a reduced dose of cefuroxime. Objective: To investigate whether the PK-PD target of cefuroxime (50%T\>MIC) is attained in the first 24 hours of treatment in adult patients on general wards with adequate and impaired renal function receiving regular and reduced doses of cefuroxime. Study design: Observational, prospective single center cohort study Study population: Adult patients (age ≥ 18 years) on general wards of Noordwest Ziekenhuisgroep (NWZ) receiving cefuroxime as part of standard care. Intervention: Three venapunctures within a period of 72 hours, containing a maximum of 18ml of venous blood in total. Main study parameters: Percentage of patients attaining the cefuroxime PK-PD target of 50%T\>MIC. This will be investigated for patients with adequate renal function receiving a regular cefuroxime dose and impaired renal function receiving a guideline recommended reduced dose. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Risks imposed by participation are considered negligible. Three venapunctures, obtaining a maximum of 18 ml venous blood are not expected to cause AEs or SAEs. Participation itself does not bring any benefit as cefuroxime treatment is part of standard care, but the group related benefit could be significant. With the results of this study, current recommended cefuroxime dosing regimens are prospectively validated or an advice to reconsider current guidelines will be obtained.

Conditions

Infection, Bacterial; Kinesics

Keywords

cefuroxim; renal function; target attainment; infectious disease

Outcome Measures

Primary Outcomes (1)

• Target Attainment

  Main study parameter is the percentage of the study population attaining the target of 50%T\>MIC within the first 24hrs of treatment. To calculate this endpoint cefuroxime concentrations and MIC-values will be obtained.

  0-24hours after treatment initiation

Secondary Outcomes (1)

• Target Attainment

  0-48hours after treatment initiation

Study Arms (2)

Adequate renal function

OTHER

Patients with adequate renal function (egfr\>30ml/min) receiving a regular cefuroxime dose

Diagnostic Test: Venapunction

Impaired renal function

OTHER

Patients with impaired renal function (egfr\<30ml/min) receiving a guideline recommended reduced dose

Diagnostic Test: Venapunction

Interventions

Venapunction DIAGNOSTIC_TEST

Three venapunctures within a period of 72 hours, containing a maximum of 18ml of venous blood in total.

Adequate renal function; Impaired renal function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Receiving cefuroxime therapy intravenous (iv) as part of standard care
• Age ≥ 18 years
• Admitted to a general ward of Noordwest Ziekenhuisgroep - location Alkmaar
• Informed consent is obtained

You may not qualify if:

• Mentally incapacitated patients, i.e. a minor or legally incompetent adult
• Renal replacement therapy during treatment with cefuroxime
• Patients admitted to the intensive care unit (ICU)
• Severely burned patients, defined as a burned surface ≥ 10%
• Patients with cystic fibrosis
• Informed consent is not obtained

Sponsors & Collaborators

• Noordwest Ziekenhuisgroep: lead

Study Sites (1)

Noordwest Ziekenhuisgroep

Alkmaar, North Holland, 1815JD, Netherlands

RECRUITING

MeSH Terms

Conditions

Bacterial Infections; Kinesics; Communicable Diseases

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Nonverbal Communication; Communication; Behavior; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Saskia E Zieck, MSc

CONTACT

0031880857476; se.zieck@nwz.nl

Ingrid MM van Haelst, PhD

CONTACT

0031880853571; i.van.haelst@nwz.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating investigor

Model Details: Percentage of patients attaining the cefuroxime PK-PD target of 50%T\>MIC. This will be investigated for patients with adequate renal function receiving a regular cefuroxime dose and impaired renal function receiving a guideline recommended reduced dose.

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 21, 2022
• Study Start: January 15, 2022
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2023
• Last Updated: April 8, 2022

Record last verified: 2022-04

Locations

NL (1)