Clinical trial NCT05971979: Therapeutic Drug Monitoring - Targeting IMproved Effectiveness
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia
Sepsis
Infection, Bacterial
Keywords: drug monitoring
sepsis
antibacterial agents
respiratory tract infections
antimicrobial stewardship
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2023-08-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Availability of LC-MS/MS results within two dose intervals of antimicrobial (dichotomous)
timeFrame: 48 hours
Secondary outcomes:
measure: Time elapsed from peripheral blood collection to LC-MS/MS result availability
timeFrame: 48 hours
measure: Time elapsed from first dose of antimicrobial to LC-MS/MS result availability
timeFrame: 72 hours
measure: Duration of pre-analytical stage
timeFrame: 24 hours
measure: Duration of analytical stage
timeFrame: 24 hours
measure: Duration of post-analytical stage
timeFrame: 24 hours
measure: Therapeutic target attainment (100% fT>4xMIC)
timeFrame: 72 hours
measure: 28-day mortality
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 28 days
measure: Hospital length of stay
timeFrame: 28 days
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital, Manchester University NHS Foundation Trust
Study officials:
affiliation: University of Manchester
name: Jan Hansel, MD
role: PRINCIPAL_INVESTIGATOR
References: