Therapeutic Drug Monitoring of Beta-lactams and Renal Hyperclearance in Patients Admitted to Intensive Care for Acute Brain Injury

NCT06999161 | Recruiting

• 1 other identifier: LOCAL/2025/CR-01
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Illness; Brain Injuries

Keywords

Beta-Lactams; Renal Clearance; Therapeutic Drug Monitoring

Outcome Measures

Primary Outcomes (1)

• Plasma betalactam underdosing

  Development of a predictive model for plasma beta-lactam underdosing in critically ill patients with acute brain injury and renal hyperclearance, receiving beta-lactam therapy for an ongoing infectious episode. Plasma beta-lactam concentrations will be measured 24 hours after initiation of antibiotic therapy, and subsequently every 48 hours, or in cases of underdosing, overdosing, antibiotic switch, or significant changes in renal function.

  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 (5)

• Evolution of Augmented Renal Clearance

  From date of inclusion until the date of discharge from intensive care, assessed up to 28 days

• Evolution of plasma Beta-lactam Concentration

  From date of inclusion until the date of discharge from intensive care, assessed up to 28 days

• Relationship Between Plasma Underdosing Intensity and Level of Augmented Renal Clearance (ARC)

  From date of inclusion until the date of discharge from intensive care, assessed up to 28 days

• Beta-lactam Dosing According to Augmented Renal Clearance Level.

  From date of inclusion until the date of discharge from intensive care, assessed up to 28 days

• Clinical outcome

  From date of inclusion until the date of discharge from intensive care, assessed up to 28 days

Study Arms (1)

BETALACTAM Treated Patients

Adult patients (≥18 years) admitted to intensive care for acute brain injury, presenting with an infectious episode, documented augmented renal clearance (as assessed by urinary creatinine clearance), and receiving treatment with beta-lactam antibiotics.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

RECRUITING

MeSH Terms

Conditions

Critical Illness; Brain Injuries

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Central Study Contacts

Claire ROGER, MD, pHD

CONTACT

+33 466683331; claire.roger@chu-nimes.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 31, 2025
• Study Start: May 5, 2025
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Locations

FR (1)