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

Sponsor

St George's, University of London (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05950984

Collaborator

University College, London (Other)

Enrollment

Location

12.1

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infection, Bacterial Antibiotic Side Effect Antibiotic Resistant Infection Sepsis Septic Shock Bacteremia Critical Illness Adult Children	Other: Drug Infusion Pump Monitoring

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Critically Ill Adults and Children Adults and children from 1-day old admitted to a critical care unit.	Other: Drug Infusion Pump Monitoring 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.

Arm

Intervention/Treatment

Critically Ill Adults and Children

Adults and children from 1-day old admitted to a critical care unit.

Other: Drug Infusion Pump Monitoring

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.

Outcome Measures

Primary Outcome Measures

Objective Function Value [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
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

Secondary Outcome Measures

Participant Vancomycin Volume of Distribution [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
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
Participant Vancomycin Clearance [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
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
Participant 24-hour Area Under the Vancomycin Concentration Time Curve (AUC) [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
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
Participant 24-hour AUC:MIC Ratio [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
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

Other Outcome Measures

Association Between Participant's Mean 24-hour AUC:MIC and Microbiological Cure [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
Microbiological cure defined as eradicated baseline microorganisms and no new microorganisms are identified via bacterial cultures (if available), plus, the patient has received allocated treatment for at least 2-days with no modification or a failure
Association Between Participant's Mean 24-hour AUC:MIC and Length of Intensive Care (ICU) Unit Stay [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
ICU stay quantified by days since admission, categories include: <2 days, < 7 days, <14 days, >14 days
Association Between Participant's Mean 24-hour AUC:MIC and Infection Related Mortality [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
Cause of mortality will be derived from participant's medical notes
Association Between Participant's Mean 24-hour AUC:MIC and Infection related ICU Re-admission [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
Cause of re-admission will be derived from participant's medical notes
Association Between Participant's Mean 24-hour AUC:MIC and Vancomycin Associated Acute Kidney Injury (AKI) [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) Criteria
Association Between Participant's Mean 24-hour AUC:MIC and Adult National Early Warning Score (NEWS2) or Paediatric Early Warning Score (PEWS3) [Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin]
Warning scores calculated on day of (and closest to) first dose of study recorded vancomycin treatment course, between 2-3 days since vancomycin course initiation and at end of vancomycin course or 28 days from first study recorded administration of vancomycin

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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