Medical Device (MD) Derived Pharmacokinetic (PK) Parameters for Vancomycin (MD-PK)

Study Overview
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Brief Summary
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Getting the right dose of antibiotic promptly is an important part of treating infections. Unfortunately, when an infection is severe (sepsis) the body changes how it processes antibiotics. Consequently, some people with severe infection retain antibiotics for too long (risking adverse effects), whilst others excrete antibiotics too quickly (risking under-treatment). Mathematical models can help researchers understand drug handling variability (known as pharmacokinetics) between people. These models require very accurate information about drug administration and drug blood concentration timings. Researchers usually rely on someone recording these timings, but recording errors can make models inaccurate. We would like to understand if using data from routinely used electronic drug infusion devices (recording the exact time of administration) can improve the accuracy of pharmacokinetic models. We intend to investigate this with an antibiotic (vancomycin) that clinicians already routinely monitor blood concentrations for. Adults and children treated at St George's Hospital intensive care units will be invited to participate in the study which will last for 28-days within a 14-month period. Participants will donate a small amount of extra blood and provide researchers access to their clinical data. Blood will be taken at special times during vancomycin treatment from lines placed as part of standard treatment, minimising any pain or distress. There will be no other changes to patient's treatment. In the future, data from this study might help change the way we dose antibiotics. The National Institute for Health and Care Research and Pharmacy Research UK are supporting the study with funding.

Official Title
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An Investigation Into How Medical Device Obtained Variables Influence the Pharmacokinetic Profile of Vancomycin: a Paediatric and Adult Critical Care Feasibility Assessment at a London Tertiary-care Hospital

Conditions
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Infection, Bacterial, Antibiotic Side Effect, Antibiotic Resistant Infection, Sepsis, Septic Shock, Bacteremia, Critical Illness, Adult Children

Intervention / Treatment
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* Other: Drug Infusion Pump Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to either adult or paediatric intensive care unit (ICU) and receiving intravenous vancomycin (continuous or intermittent infusion only), to prevent or treat a clinical infection Informed consent form signed by participant/parent/legal guardian/legal representative (as determined by age group/capacity, consent may be retrospective) or signed informed personal/nominated consultee declaration Age from 1-day since birth Exclusion Criteria: Previous enrolment into this study Treating clinician feels participant unlikely to survive beyond 48-hours from enrolment or treatment has been withdrawn for reasons of palliation Absence of in-dwelling vascular access from which samples may be drawn or removal of in-dwelling access prior to retrieval of a 3rd blood sample (for assay of vancomycin concentration) Non-continuous renal replacement (i.e. intermittent haemodialysis/ peritoneal dialysis) Hypersensitivity or allergies to vancomycin, its excipients, or the infusion fluid Treatment outside an ICU area In paediatrics: Required blood sampling exceeds 3% of total blood volume in a four-week period or 1% at any single time (European Medicines Agency, 2009) Where there is disagreement between child consent/assent and parental/ legal guardian consent/assent

Ages Eligible for Study
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Minimum Age: 1 Day

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Critically Ill Adults and Children<br>Adults and children from 1-day old admitted to a critical care unit. | Other: Drug Infusion Pump Monitoring<br>* Intravenous vancomycin administration accuracy will be determined by comparing data obtained from drug infusion pumps with manually input administration times from the electronic Prescribing and Medicines Administration (ePMA) system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Function Value | Pharmacokinetic model fit determined quantitively by Objective Function Value (2.log likelihood) using vancomycin administration time data recorded by patient's bedside drug infusion devices compared to manually recorded data | Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Vancomycin Volume of Distribution | Calculation of participant's vancomycin volume of distribution (litres) using non-linear mixed effects modelling methods from obtained non-protein bound and total vancomycin concentrations and patient's drug infusion device obtained administration time data | Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin | 
| Participant Vancomycin Clearance | Calculation of participant vancomycin clearance (litres/hour) using non-linear mixed effects modelling methods using obtained non-protein bound and total vancomycin concentrations and participant's drug infusion device derived administration time data | Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin | 
| Participant 24-hour Area Under the Vancomycin Concentration Time Curve (AUC) | Calculation of participant's AUC (milligrams.hour/litre) using obtained non-protein bound and total vancomycin concentrations and participant's drug infusion device derived administration time data | Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin | 
| Participant 24-hour AUC:MIC Ratio | Calculation of the area under the 24-hour non-protein bound and total vancomycin concentration AUC/bacterial minimum inhibitory concentration (MIC) ratio using an empiric MIC of 1mg/L or MIC of obtained isolates (if available) using trapezial rule or vancomycin dose and calculated clearance | Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vancomycin, Pharmacokinetics, Accuracy, Medical Device, Digital, Data, Protein Binding, Critical Illness, Drug Infusion Pump, Electronic Prescribing and Administration System, Point of Care, Therapeutic Drug Monitoring