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

• ClinicalTrials.gov Identifier: NCT05950984
• Recruitment Status: Recruiting
• First Posted: July 18, 2023
• Last Update Posted: January 11, 2024
• Sponsor: St George's, University of London
• Collaborator: University College, London
• Information provided by (Responsible Party): St George's, University of London

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
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
• Estimated 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
• Actual Study Start Date: October 30, 2023
• Estimated Primary Completion Date: July 2024
• Estimated Study Completion Date: August 2024

Groups and Cohorts

Group/Cohort	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 :

1. Objective Function Value [ Time Frame: 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 :

1. Participant Vancomycin Volume of Distribution [ Time Frame: 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
2. Participant Vancomycin Clearance [ Time Frame: 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
3. Participant 24-hour Area Under the Vancomycin Concentration Time Curve (AUC) [ Time Frame: 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
4. Participant 24-hour AUC:MIC Ratio [ Time Frame: 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:

1. Association Between Participant's Mean 24-hour AUC:MIC and Microbiological Cure [ Time Frame: 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
2. Association Between Participant's Mean 24-hour AUC:MIC and Length of Intensive Care (ICU) Unit Stay [ Time Frame: 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
3. Association Between Participant's Mean 24-hour AUC:MIC and Infection Related Mortality [ Time Frame: 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
4. Association Between Participant's Mean 24-hour AUC:MIC and Infection related ICU Re-admission [ Time Frame: 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
5. Association Between Participant's Mean 24-hour AUC:MIC and Vancomycin Associated Acute Kidney Injury (AKI) [ Time Frame: 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
6. Association Between Participant's Mean 24-hour AUC:MIC and Adult National Early Warning Score (NEWS2) or Paediatric Early Warning Score (PEWS3) [ Time Frame: 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

• Ages Eligible for Study: 1 Day and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

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

Contacts and Locations

Contacts

Contact: Robert Oakley, MPharm; 02086721255 ext 3685; robert.oakley@nhs.net

Contact: Dagan Lonsdale, MB BS, PhD; 02087250205; dlonsdal@sgul.ac.uk

Locations

United Kingdom

St Georges University Hospitals NHS Foundation Trust; Recruiting

London, United Kingdom, SW17 0QT

Contact: Robert Oakley, MPharm 02086721255 ext 3685 robert.oakley@nhs.net

Contact: Dagan Lonsdale, MB BS, PhD 02087250205 dlonsdal@sgul.ac.uk

Principal Investigator: Dagan Lonsdale, MB BS, PhD

Sponsors and Collaborators

St George's, University of London

University College, London

More Information

Publications:

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

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.

• Responsible Party: St George's, University of London
• ClinicalTrials.gov Identifier: NCT05950984
• Other Study ID Numbers: 2022.0286
• First Posted: July 18, 2023
• Last Update Posted: January 11, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Fully anonymised collected patient data may be shared if consent provided with select research collaborators

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St George's, University of London:

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

Additional relevant MeSH terms:

Infections; Communicable Diseases; Bacteremia; Bacterial Infections; Critical Illness; Disease Attributes; Pathologic Processes; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses