E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: • To investigate whether the current dosing regimen of cefuroxime, recommended by the SWAB guideline and applied at Noordwest Ziekenhuisgroep for adult patients with various degrees of renal function on general wards, results in PK-PD target attainment of 50%T>MIC after 24-48 hours of therapy. • To investigate whether the current dosing regimen of cefuroxime, recommended by the SWAB guideline and applied at Noordwest Ziekenhuisgroep for adult patients with various degrees of renal function on general wards, results in PK-PD target attainment of 100%T>MIC during the first 24 hours of therapy. • To compare cefuroxime exposure at 24 hours and 24-48 hours after start of treatment between three different renal function groups in terms of AUC and Cmin: o Group A: eGFR ≥30ml/min/1.73m2 treated with standard doses of cefuroxime o Group B: eGFR 29-10ml/min/1.73m2 treated with reduced doses of cefuroxime |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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 |
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E.4 | Principal exclusion criteria |
• 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PK-PD target attainment in the first 24 hours after start of treatment with cefuroxime. To be able to define this endpoint, ideal sampling occurs within 24 hours after the initiation of treatment with cefuroxime, however sampling until 72 hours after treatment will inform us about target attainment in the first 24 hours of treatment. By using population pharmacokinetic modelling, PK-PD target attainment in the first 24 hours of treatment can also be investigated using samples that are collected shortly after this period, assuming PK is not likely to change rapidly in patients admitted to a general ward (in contrast to patients who need intensive care). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
50%T>MIC after 24-48 hours of therapy, 100%T>MIC during the first 24 hours of therapy, AUC and Cmin will be investigated comparable with investigating the main study parameter, as described above (E.5.1 ). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |