Clinical trial NCT05950984: Medical Device (MD) Derived Pharmacokinetic (PK) Parameters for Vancomycin (MD-PK)
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infection, Bacterial
Antibiotic Side Effect
Antibiotic Resistant Infection
Sepsis
Septic Shock
Bacteremia
Critical Illness
Adult Children
Keywords: 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
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: University College, London
First posted: 2023-07-18
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults and children admitted to an intensive care unit and administered intravenous vancomycin for prevention/treatment of an infection

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Function Value
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
Secondary outcomes:
measure: Participant Vancomycin Volume of Distribution
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Participant Vancomycin Clearance
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Participant 24-hour Area Under the Vancomycin Concentration Time Curve (AUC)
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Participant 24-hour AUC:MIC Ratio
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
Other outcomes:
measure: Association Between Participant's Mean 24-hour AUC:MIC and Microbiological Cure
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Association Between Participant's Mean 24-hour AUC:MIC and Length of Intensive Care (ICU) Unit Stay
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Association Between Participant's Mean 24-hour AUC:MIC and Infection Related Mortality
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Association Between Participant's Mean 24-hour AUC:MIC and Infection related ICU Re-admission
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Association Between Participant's Mean 24-hour AUC:MIC and Vancomycin Associated Acute Kidney Injury (AKI)
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
measure: Association Between Participant's Mean 24-hour AUC:MIC and Adult National Early Warning Score (NEWS2) or Paediatric Early Warning Score (PEWS3)
timeFrame: Within collection of 15 vancomycin serum concentrations or 28 days from first study recorded administration of vancomycin
Locations:
city: London
country: United Kingdom
facility: St Georges University Hospitals NHS Foundation Trust
Study officials:
References:
citation: Oakley R, Bakrania P, Yau T, Standing J, Lonsdale D. Variable adherence to and effectiveness of a vancomycin continuous infusion protocol within ICUs at a London tertiary-care hospital: a single-centre retrospective service evaluation 2022;4:dlac004.036. https://doi.org/10.1093/jacamr/dlac004.036
citation: Correction to: Improving adherence to and effectiveness of an adult critical care vancomycin continuous infusion protocol: a pilot quality improvement and administration data accuracy project. JAC Antimicrob Resist. 2023 Jun 8;5(3):dlad075. doi: 10.1093/jacamr/dlad075. eCollection 2023 Jun.