PK/PD Target Attainment of Ceftriaxone for the Prevention of Early Ventilator-associated Pneumonia in Neurologically Injured Patients (NeuroPKVAP)

Critically ill patients admitted for acute brain injury are exposed to many heath-care associated infections such as ventilator associated pneumoniae (VAP). The PROHYVAP study, published in 2024 reported that a single dose of CEFTRIAXONE as an antibiotic prophylaxis could reduce the incidence of early VAP (VAP that occured between day 2 and day 7 of mechanical ventilation).

However, patients with acute brain injury also presented frequently augmented renal clearance (ARC), which could affect the pharmacokinetic and pharmacodynamic target attainment (PK/PD) of antibiotic prophylaxis.

This study aims to analyse the PK/PD target attainment after one dose of CEFTRIAXONE in critically ill patients with acute brain injury and to describe the effect of ARC on PK/PD target attainment during early VAP.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Brain Injuries; Early Ventilator Associated Pneumonia

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Maureen Steib, MD; Phone Number: +33 3 83 85 10 45; Email: m.steib@chru-nancy.fr

Study Locations

• France
  • Lorraine
    • Nancy, Lorraine, France, 54000
      • CHRU de Nancy - Hôpital Central
  • Meurthe-et-Moselle
    • Nancy, Meurthe-et-Moselle, France, 54000
      • CHRU Nancy - Hôpital Central
      • Contact: Maureen STEIB; Phone Number: +33 3 83 85 10 45; Email: m.steib@chru-nancy.fr
      • Contact: Viviane MARTIN, PhD; Email: v.martin3@chru-nancy.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients admitted in intensive care unit for an acute brain injury caused by a traumatic brain injury or a vascular cerebral disease (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage) with a Glasgow coma scale < 12 and needed a mechanical ventilation for 48 hours or more, started in the first 12 hours.

Description

Inclusion Criteria:

• 18 years or older
• Admitted in intensive care unit for acute brain injury, including traumatic brain injury and cerebral vascular disease
• Glasgow coma scale inferior to 12
• Orotracheal intubation in first 12 hours of admission
• Needed of invasive mechanical ventilation for at least 48 hours

Exclusion Criteria:

• Acute brain injury related to tumoral or infectious process
• Antibiotic therapy administered before acute brain injury for an other pathology
• Patients with a risk of multiresistance bacteria contamination (stay in a risk area in the past 3 months, antibiotic therapy with fluoroquinolone or betalctamine in the past 3 months, hospitalization in last month before admission, documented contaminationwith multiresistance bacteria, immunodepression)
• Patients with hish risk of death in the first 48 hours
• Patients with a beta-lactams reported allergy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Critically ill patients with acute brain injury; Patients with severe acute brain injury defined by a Glasgow coma scale < or = 8, admitted to the intensive care unit and needed invasive mechanical ventilation for at least 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with PK/PD target attainment	Proportion of patients with serum concentrations of CEFTRIAXONE above the minimal inhibitory concentration (MIC) of 4 mg/mL (in case of undocumented VAP), or > 4 times the MIC of documented bacteria.	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Impact of the PK/PD target attainment on the incidence of early ventilator associated pneumoniae	Day 7
Association between augmented renal clearance and PK/PD target attainment	24 hours
Association between hyperbilirubinemia and PK/PD target attainment	24 hours
Association between PK/PD target attainment and day 28 mortality	Day 28
Association between PK/PD target attainment and ICU length of stay	3 months
Incidence of multi drug resistance bacteria	Day 28

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Study Director: Emmanuel NOVY, MD,PhD, Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ventilator associated pneumonia; Antibiotic prophylaxis; augmented renal clearance; PK/PD target attainment
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Craniocerebral Trauma; Trauma, Nervous System; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Brain Injuries; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: 2025PI164

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