Clinical trial NCT06999161: Therapeutic Drug Monitoring of Beta-lactams and Renal Hyperclearance in Patients Admitted to Intensive Care for Acute Brain Injury
Official title: Therapeutic Drug Monitoring of Beta-lactams and Renal Hyperclearance in Patients Admitted to Intensive Care for Acute Brain Injury
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Critical Illness
Brain Injuries
Keywords: Beta-Lactams
Renal Clearance
Therapeutic Drug Monitoring
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2025-05-31
Enrollment: 140
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: The population studied included patients admitted to the intensive care unit with acute brain injury (of traumatic, vascular, infectious or immunological origin), presenting a profile of HCR and receiving antibiotic treatment with betalactam

Brief summary: Augmented Renal Clearance (ARC), defined as a supraphysiological increase in renal function, is frequently observed in critically ill patients, particularly those with acute brain injury. ARC complicates the management of renally eliminated drugs, specifically beta-lactam antibiotics, by enhancing drug clearance and thereby increasing the risk of underdosing and therapeutic failure. Although pharmacological therapeutic drug monitoring (TDM) is recommended to optimize dosing, it remains limited by issues of accessibility, highlighting the need for alternative approaches to identify at-risk patients and adjust dosing based on renal function.

Early identification of patients at risk for subtherapeutic beta-lactam plasma concentrations could enable timely dose adjustments. A combined assessment of renal function and beta-lactam TDM could enhance our understanding of the kinetics of both parameters. These data may support the development of predictive models capable of proposing individualized dosing regimens based on renal function.

Optimizing beta-lactam plasma concentrations in this patient population could improve infection management and potentially enhance clinical outcomes.


Eligibility criteria: Inclusion Criteria:

* Adult patients (≥18 years old)
* Admitted to the intensive care unit for acute brain injury
* Exhibiting Augmented Renal Clearance (ARC), defined by a urinary creatinine clearance (ClCrU) greater than 130 mL/min/1.73 m² on at least one measurement
* Receiving Therapeutic Drug Monitoring (TDM)-guided treatment with one of the following beta-lactam antibiotics: amoxicillin/clavulanic acid, cefotaxime, piperacillin/tazobactam, cefepime, or meropenem
* Affiliated with or benefiting from a health insurance scheme

Exclusion Criteria:

* Estimated life expectancy \<24 hours
* Patients who have expressed opposition to study participation
* Patients under legal protection (guardianship, curatorship, or court protection)
* Patients currently in an exclusion period determined by participation in another study
* Patients already enrolled in a study that precludes concurrent participation in an observational study

Primary outcomes:
measure: Plasma betalactam underdosing
timeFrame: 24 hours after the start of antibiotic therapy, and repeated every 48 hours or in the event of underdosing, overdosing, change of molecule or significant variation in renal function, assessed until the antibiotic therapy is stopped, for up to 14 days
Secondary outcomes:
measure: Evolution of Augmented Renal Clearance
timeFrame: From date of inclusion until the date of discharge from intensive care, assessed up to 28 days
measure: Evolution of plasma Beta-lactam Concentration
timeFrame: From date of inclusion until the date of discharge from intensive care, assessed up to 28 days
measure: Relationship Between Plasma Underdosing Intensity and Level of Augmented Renal Clearance (ARC)
timeFrame: From date of inclusion until the date of discharge from intensive care, assessed up to 28 days
measure: Beta-lactam Dosing According to Augmented Renal Clearance Level.
timeFrame: From date of inclusion until the date of discharge from intensive care, assessed up to 28 days
measure: Clinical outcome
timeFrame: From date of inclusion until the date of discharge from intensive care, assessed up to 28 days
Other outcomes:
Locations:
city: Nîmes Cedex 09
country: France
facility: CHU de Nîmes - Hôpital Universitaire Carémeau
Study officials:
References: