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NCT Number: NCT06999161

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

Location status: Recruiting

Location contact

Claire ROGER, MD, PhD

CONTACT

Claire ROGER, MD, PhD

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Plasma betalactam underdosing

    Time frame: 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

    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.

Secondary outcomes

  1. Evolution of Augmented Renal Clearance

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

    Assessment of urinary creatinine clearance based on urine collection (8, 12, or 24-hour collection depending on center practices).

  2. Evolution of plasma Beta-lactam Concentration

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

    Monitoring of total plasma beta-lactam concentrations obtained through Therapeutic Drug Monitoring during the intensive care stay

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

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

    Characterization of the intensity of plasma beta-lactam underdosing for each antibiotic molecule relative to the degree of ARC.

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

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

    Development of a dosing nomogram for beta-lactam antibiotics tailored to the degree of ARC.

  5. Clinical outcome

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

    Assessment of clinical outcomes based on rates of clinical success and failure.

    • Clinical success is defined as the resolution of infectious symptoms present at the initiation of antibiotic therapy, allowing discontinuation of antibiotics at the end of the planned treatment duration.
    • Clinical failure is defined as the persistence or worsening of initial symptoms, the occurrence of superinfection (infection with newly identified pathogens), or recurrence (a new infectious episode with the same pathogen).

Study contacts

Contact information is provided by the study sponsor or research team.

Claire ROGER, MD, pHD

CONTACT

[email protected]

+33 466683331

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Registry information

Acronym: BETALACT-ARC

Important dates

Study start
2025
Primary completion
2025
Study completion
2025
First posted
May 31, 2025
Registry last updated
May 31, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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