TDM-optimized Teicoplanin Dosing Versus Standard of Care

Study Overview
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Brief Summary
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Value of TDM for teicoplanin is not well defined. In this single-center low-interventional randomized trial the investigators aim to investigate the superiority of teicoplanin TDM-optimized using Model-Informed-Precision-Dosing (MIPD) of unbound concentrations versus the standard of care (dosing based on antibiotic guidelines) in target attainment.

Detailed Description
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Teicoplanin is a glycopeptide antibiotic that is frequently used in the treatment of gram-positive bacterial infections. The glycopeptide antibiotic vancomycin is currently the first choice of treatment against methicillin-resistant Staphylococcus aureus (MRSA), but teicoplanin is found to have a similar efficacy while showing less nephrotoxicity (4.8% vs 10.7%). Vancomycin dosing is based on therapeutic drug monitoring (TDM). In contrast to vancomycin, value of TDM for teicoplanin is not as well defined. In this study the superiority of teicoplanin TDM-optimized dosing using Model-Informed-Precision-Dosing (MIPD) of unbound concentrations versus the standard of care (dosing based on antibiotic guidelines) in target attainment will be investigated. The overall aim of this research is to improve antibiotic treatment with teicoplanin to allow safe and optimal treatment of glycopeptide susceptible strains and to prevent de novo development of resistance.

Official Title
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A Randomized Trial Investigating the Superiority of TDM-optimized Teicoplanin Dosing Versus Standard of Care

Conditions
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Bacterial Infections

Intervention / Treatment
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* Drug: Teicoplanin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is admitted to the ICU, haematology, gastroenterology or orthopaedics department. The patient is at least 18 years old on the day of inclusion. The patient is treated with teicoplanin as part of standard care. The patient or a representative is willing to sign the Informed Consent Form Exclusion Criteria: The patient has previously participated in this study. The patient receives any form of renal replacement criteria (RRT) other than CVVHD / CVVHDF. Expected duration of teicoplanin therapy is less than 5 days. The patient is pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 between standard treatment and treatment guided by TDM with MIPD.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care<br>Participants receive teicoplanin on discretion of the doctor | |
| Experimental: Model Informed Precision Dosing (MIPD) guided Therapeutic Drug Monitoring(TDM)<br>Participants start on standard of care dosing. After 2 days blood samples will be analysed and exposure will be determined using MIPD. Wherever necessary dose adjustments will be made. | Drug: Teicoplanin<br>* Dose will be adjusted in the study arm using MIPD guided TDM- dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of participants that reaches therapeutic exposure after 5 days of treatment | Unbound teicoplanin exposure after 5 days will be determined and compared to the predefined therapeutic window of 70-150 mg/L*24h | 5-7 days after initiation of teicoplanin therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until reaching target attainment | Time until a participant reaches the therapeutic window will be estimated using the MIPD | 5-7 days after initiation of teicoplanin therapy | 
| Clinical failure | Incidence of clinical failure at day 30. Incidence of clinical failure of teicoplanin treatment will be defined as occurrence of one of the following on day 30: Persistent bacteremia Uncontrolled infection at the site of infection by the pathogen for which teicoplanin treatment was started Escalation of therapy Switch of antimicrobial therapy due to lack of effectiveness of teicoplanin | 30 days after initiation of teicoplanin therapy | 
| Days in hospital | Total number of days in the hospital | 30 days after initiation of teicoplanin therapy |