Therapeutic Drug Monitoring - Targeting IMproved Effectiveness (TDM-TIME)

Therapeutic Drug Monitoring - Targeting Improved Effectiveness (TDM-TIME): An Observational Study of Turnaround Time for Therapeutic Drug Monitoring of Antimicrobial Agents in Critically Ill Patients With Respiratory Sepsis

Severe infections can be caused by various organisms, such as bacteria or viruses, and lead to otherwise healthy people getting very unwell, sometimes needing treatment in hospital or even intensive care. For the treatment of bacterial infections to be successful, the correct antibiotics need to be given promptly. Early in the course of illness, clinicians often do not know exactly which bacteria are causing the infection. Furthermore, patients differ in terms of how their bodies process the antibiotics they are given; this means that some may get too much and others too little. This can in turn lead to some patients not being fully cured, and others coming to harm due to side effects of higher doses of these drugs.

For certain types of antibiotics, clinicians are able to measure their levels in the bloodstream, which can help guide dosing. This is called therapeutic drug monitoring, and is commonly used in clinical practice. One of the problems with therapeutic drug monitoring is that it is often not available outside of regular working hours, is costly, and most importantly, provides clinicians with useful information only after a few days of treatment have already been completed. This may be too late to treat these severely ill patients with life-threatening infections, where early and appropriate treatments matter.

The aim of our study, called TDM-TIME, is to look at how long it takes for blood samples to get from the patient to the laboratory to be measured, with the results then communicated back to clinicians. We are further looking to investigate whether steps can be taken to improve these timings, which would lead to shorter times until treatments can be improved. As our study is observational, we will not change anything about the treatment of our patients, but will only be measuring levels of antibiotics in their blood.

Study Overview

• Status: Recruiting
• Conditions: Pneumonia; Sepsis; Infection, Bacterial
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Lynne Webster; Phone Number: +441617015057; Email: research.sponsor@mft.nhs.uk

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • Wythenshawe Hospital, Manchester University NHS Foundation Trust
    • Contact: Jan Hansel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation except where the study inclusion and exclusion criteria explicitly state otherwise.

Description

Inclusion Criteria:

• Age > 18 years;
• Admitted to intensive care;
• Treated for presumed or confirmed lower respiratory tract infection;
• Receiving OR about to receive the first dose of intravenous antimicrobials (either meropenem of piperacillin/tazobactam);
• Valid informed consent OR enrolment through deferred consent appropriate.

Exclusion Criteria:

• Severe anaemia (haemoglobin level < 70 g/L);
• Unlikely to survive 24 hours as judged by the treating physician;
• Study antimicrobial course started more than 24 hours ago.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critically ill patients with presumed or confirmed lower respiratory tract infection; Non-interventional. Admitted to intensive care unit. Presumed or confirmed lower respiratory tract infection. Receiving either piperacillin/tazobactam or meropenem. Participants will have samples collected during an antimicrobial dose cycle.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Availability of LC-MS/MS results within two dose intervals of antimicrobial (dichotomous)	Proportion of participants within timeframe for antimicrobial	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time elapsed from peripheral blood collection to LC-MS/MS result availability	Mean time required for result availability	48 hours
Time elapsed from first dose of antimicrobial to LC-MS/MS result availability	Mean time required for result availability from first antimicrobial dose administration	72 hours
Duration of pre-analytical stage	Mean time required for pre-analytical stage	24 hours
Duration of analytical stage	Mean time required for analytical stage	24 hours
Duration of post-analytical stage	Mean time required for post-analytical stage	24 hours
Therapeutic target attainment (100% fT>4xMIC)	Proportion of patients attaining target (100% fT>4xMIC)	72 hours
28-day mortality	Proportion of patients alive at 28 days from enrolment	28 days
ICU length of stay	Number of days from ICU admission to discharge	28 days
Hospital length of stay	Number of days from hospital admission to discharge	28 days

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Investigators: Principal Investigator: Jan Hansel, MD, University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): May 15, 2024

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: sepsis; antimicrobial stewardship; respiratory tract infections; drug monitoring; antibacterial agents
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Bacterial Infections
• Other Study ID Numbers: B01949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No