Early Optimization of Ceftazidime Regimen in Critical Care

NCT07085624 | Not Yet Recruiting

• 2 other identifiers: 24PH176_12024-519783-41-00
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 8

Brief Summary

Hospital-acquired infections, most of which are caused by Gram-negative bacteria, are common in intensive care units and have a major impact on patient prognosis. Patient survival in severe sepsis and septic shock depends on the early administration of appropriate antibiotic therapy, with mortality increasing by 7.6% for each hour of delay, justifying the probabilistic use of broad-spectrum antibiotics such as ceftazidime, an essential betalactamine, particularly used for its activity against Pseudomonas aeruginosa, a frequent pathogen in nosocomial infections. It is currently recommended that ceftazidime should initially be administered as a 2g loading dose, followed by maintenance treatment by continuous infusion, at a dose adapted to renal function. The recommended dosage regimen, with its 2g loading dose, was developed using the median value of parameters from a pharmacokinetic model. This explains the findings of many critical care studies, which have found that 40-60% of patients initially have concentrations below target with the recommended dosing regimen. In the context of critical care, maintaining concentrations within the target therapeutic range is difficult due to variations in the elimination clearance of ceftazidime. Ceftazidime is mainly eliminated by the kidneys. Critical patients may have increased glomerular filtration rate, or, conversely, impaired renal function, with rapid variations in the event of severe infection. This leads to high intra- and inter-individual variability, and increases the risk of antibiotic under- or overdose when the maintenance dose is administered at a fixed dose (6g/d continuously). This high variability can also be observed in the volume of distribution (capillary leakage, oedema, perfusion volumes, effusions ...). In order to propose an individualised dosing regimen, we therefore propose an iterative randomised study to :

• Step 1: FORTOPTIM\_1 Evaluation of an optimised dosage regimen based on literature data compared with the standard psological regimen.
• Step 2: FORTOPTIM\_2 Build a pharmacokinetic model from the prospective data obtained in step 1. Based on this model, an individualised dosage regimen (loading dose and maintenance dose) will be obtained for step 3.
• Step 3: FORTOPTIM\_3 Prospectively evaluate in a randomised trial the individualised dosing regimen previously defined (Step 2) by comparing it to the best dosing regimen determined in Step 1 or to the standard dosing regimen if there is no significant difference in Step 1.

Conditions

Infection in ICU; Sepsis; Septic Shock; Pseudomonas Aeruginosa Infection

Keywords

ceftazidime; intensive care unit; pharmacokinetics; individualised dosing regimen

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects with a ceftazidime concentration equal to or above the target concentration threshold (35 mg/L) at both 3h and 24h after the first administration, and below the toxicity threshold of 100 mg/L.

  24 hours

Secondary Outcomes (6)

• Patient severity assessed using the SOFA (Sequential Organ Failure Assessment Score)

  day 7

• death

  day 28

• Occurrence of neurological adverse events defined as: seizure, myoclonus, encephalopathy or delirium, altered consciousness (Glasgow score)

  day 28

• Occurrence of an overdose defined as a concentration greater than 100 mg/L.

  day 28

• Renal function assessment

  day 28

Study Arms (2)

ceftazidime standard dosage regimen

ACTIVE COMPARATOR

Loading dose 2g Maintenance dose : 6g/d if GFR (Glomerular Filtration Rate) ≥ 60 3g/d if GFR between 30 and 60 1.5g/d if GFR between 15 and 30

Drug: ceftazidime; Biological: plasma ceftazidime dosage

ceftazidime optimised dosage regimen

EXPERIMENTAL

Loading dose 4g Maintenance dose : 6g/d if GFR (Glomerular Filtration Rate) ≥ 60 3g/d if GFR between 30 and 60 1.5g/d if GFR between 15 and 30

Drug: ceftazidime; Biological: plasma ceftazidime dosage

Interventions

ceftazidime DRUG

ceftazidime loading dose and maintenance dose

ceftazidime optimised dosage regimen; ceftazidime standard dosage regimen

plasma ceftazidime dosage BIOLOGICAL

plasma ceftazidime dosage kinetics will be performed according to an optimal D- sampling plan (4 measurements per subject: T0+5min, T0+3h, T0+6h, T0+24h, PFIM software). T0 corresponds to the time to administer the ceftazidime loading dose.

ceftazidime optimised dosage regimen; ceftazidime standard dosage regimen

Eligibility Criteria

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

You may not qualify if:

• Pregnant woman, parturient, nursing mother;
• Person deprived of liberty, hospitalized without consent,
• Adults under legal protection (guardianship-curatorship)
• Patients undergoing extra-renal purification or whose CKD-EPI at the start of treatment is less than 15 ml/min.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Direction Générale de l'Offre de Soins: collaborator
• GIRCI Auvergne Rhône-Alpes: collaborator

Study Sites (8)

CHU GRENOBLE, Médecine intensive

Grenoble, 38043, France

Location

HCL Croix Rousse, Médecine intensive réanimation

Lyon, 69004, France

Location

HCL Hôpital Edouard Herriot, Médecine intensive et réanimation

Lyon, 69437, France

Location

CHU Nord, Médecine intensive et réanimation

Marseille, 13915, France

Location

HCL Hôpital Lyon Sud, Médecine intensive réanimation

Pierre-Bénite, 69495, France

Location

CHU ST-ETIENNE - Médeine Intensive Réanimation

Saint-Etienne, 42055, France

Location

CHU ST-ETIENNE, Médecine intensive Réanimation B

Saint-Etienne, 42055, France

Location

CHU ST-ETIENNE, Réanimation Néphrologie

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic; Pseudomonas Infections

Interventions

Ceftazidime

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Cephaloridine; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Sophie PERINEL-RAGEY, MD PhD

CONTACT

(0)4 77 82 94 36; sophie.perinel.ragey@univ-st-etienne.fr

Carine LABRUYERE

CONTACT

(0)4 77 12 04 69; carine.labruyere@chu-st-etienne.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization comparing 2 therapeutic strategies

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: July 25, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

FR (8)