Early Optimization of Ceftazidime Regimen in Critical Care

NCT ID: NCT07085624

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2026-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ceftazidime standard dosage regimen

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

Group Type: ACTIVE_COMPARATOR

plasma ceftazidime dosage

Intervention Type: 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

Intervention Type: DRUG

ceftazidime loading dose and maintenance dose

ceftazidime optimised dosage regimen

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

Group Type: EXPERIMENTAL

plasma ceftazidime dosage

Intervention Type: 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

Intervention Type: DRUG

ceftazidime loading dose and maintenance dose

Interventions

plasma ceftazidime dosage

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.

Intervention Type: BIOLOGICAL

ceftazidime

ceftazidime loading dose and maintenance dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient hospitalized in intensive care unit for an expected duration of at least 72 hours, with an infection for which initiation of ceftazidime therapy is being considered.
• Patient with an arterial catheter for blood sampling.
• Patients affiliated to or entitled under a social security scheme.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Direction Générale de l'Offre de Soins

OTHER_GOV

Sponsor Role: collaborator

GIRCI Auvergne Rhône-Alpes

UNKNOWN

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU GRENOBLE, Médecine intensive

Grenoble, , France

HCL Croix Rousse, Médecine intensive réanimation

Lyon, , France

HCL Hôpital Edouard Herriot, Médecine intensive et réanimation

Lyon, , France

CHU Nord, Médecine intensive et réanimation

Marseille, , France

HCL Hôpital Lyon Sud, Médecine intensive réanimation

Pierre-Bénite, , France

CHU ST-ETIENNE - Médeine Intensive Réanimation

Saint-Etienne, , France

CHU ST-ETIENNE, Médecine intensive Réanimation B

Saint-Etienne, , France

CHU ST-ETIENNE, Réanimation Néphrologie

Saint-Etienne, , France

Countries

France

Central Contacts

Sophie PERINEL-RAGEY, MD PhD

Role: CONTACT

sophie.perinel.ragey@univ-st-etienne.fr

(0)4 77 82 94 36

Carine LABRUYERE

Role: CONTACT

carine.labruyere@chu-st-etienne.fr

(0)4 77 12 04 69

Facility Contacts

Guillaume MD DUMAS

Role: primary

GDumasgalant@chu-grenoble.fr

+33476767021

Hodane MD YONIS

Role: primary

Hodane.yonis@chu-lyon.fr

+33426109271

Laurent PhD ARGAUD

Role: primary

laurent.argaud@chu-lyon.fr

+33472112862

Sami PhD HRAIECH

Role: primary

sami.hraiech@ap-hm.fr

+33491965836

Auguste MD DARGENT

Role: primary

auguste.dargent@chu-lyon.fr

+33478862006

Sophie MD, PhD PERINEL-RAGEY

Role: primary

sophie.perinel.ragey@univ-st-etienne.fr

(0)4 77 82 94 36

Jérôme MOREL, MDPhD

Role: primary

jerome.morel@chu-st-etienne.fr

+33477828329

Christophe MD PhD MARIAT

Role: primary

christophe.mariat@chu-st-etienne.fr

+33477828345

Other Identifiers

2024-519783-41-00

Identifier Type: CTIS

Identifier Source: secondary_id

24PH176_1

Identifier Type: -

Identifier Source: org_study_id