Lung Concentrations of Ceftazidime in Patients With Ventilator-associated Pneumonia

Pneumonia Clinical Trial

— CEFTALC  

Official title:

Comparison of Lung Concentrations of Ceftazidime Administered by Continuous Versus Intermittent Infusion in Patients With Ventilator-associated Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02837835
• Other study ID #: 104R04
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2016
• Last updated: July 15, 2016
• Start date: March 2005
• Est. completion date: February 2008

Study information

• Verified date: July 2016
• Source: CHU de Reims
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal effect. Numerous arguments are in favor of continuous administration of ceftazidime, both for reasons of clinical efficacy and to preserve bacteriological mutation. The investigators report a prospective, single-center, parallel-group, randomized, controlled trial comparing two modes of administration of ceftazidime, namely, continuous administration (loading dose of 20 mg/kg of body weight followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg over 30 min every 8 h) in 34 patients with ventilator-associated pneumonia due to Gram-negative bacilli. The study was performed over 48 h with 13 and 18 assessments of serum ceftazidime in the continuous-infusion group (group A) and the intermittent-fusion group (group B), respectively. Bronchoalveolar lavage (BAL) was performed at steady state in both groups at 44 h to determine ceftazidime levels in the epithelial lining fluid. The investigators chose a predefined threshold of 20 mg/liter for serum concentrations of ceftazidime because of ecological conditions in our center.

Description:

Primary objective

The main objective of this study is to show the continuous administration of superiority ceftazidime versus intermittent administration, in terms of lung tissue concentration of ceftazidime in mechanically ventilated patients with pneumonia caused by a bacillus gram negative.

Methods

Trial

Prospective therapeutic trial in parallel groups, controlled, randomized, single center comparing two methods of administration of ceftazidime (continuous administration by self-pulsed syringe versus discontinuous administration regimens to 3 injections per 24 hours) in patients with severe pneumonia in mechanically ventilated due to gram negative bacillus.

Population

Patients will be enrolled in the Intensive Care Unit of the Reims university hospital.

All patients meeting the inclusion criteria and respecting the criteria of non-inclusions (see below) will be consecutively enrolled in the study after obtaining consent. The allocation of one of the 2 treatment modality will be made by randomization.

Variables and parameters collected in the study:

In addition to sociodemographic variables, variables for inclusion in the study and judgment criteria, different blood and urine tests will be collected:

1. Criteria for inclusion and non-inclusion (see above);

2. Outcome:

i) concentration in the cell film ceftazidime;

ii) serum concentration of ceftazidime;

iii) period during which the serum concentration of ceftazidime is higher than 20 mg/l;

3. Socio-demographic variables: Age, Gender;

4. Blood Assays: Blood gas; Blood Urea, créatinimémie and chemistry panel; serum protein; Complete Blood Count; Beta HCG if women of childbearing age; Liver function tests: AST, ALT, GGT, bilirubin, alkaline phosphatase;

5. Urinary Assays: Creatinine clearance and urinary electrolytes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Age >18 years;

• Patients hospitalized in the general intensive care unit of the University Hospital of Reims;

• Nosocomial pneumonia with Gram-negative.

Exclusion Criteria:

• Weight >110 kg;

• Pregnant or breastfeeding women;

• Known allergy to beta - lactam antibiotics;

• Renal impairment: clearance <60 calculated by the Cockcroft and Gault;

• Known history of pulmonary fibrosis;

• Patients included in another research protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated

Intervention

Drug:
• ceftazidime
20 mg/kg of body weight followed by 60 mg/kg/day
• ceftazidime
20 mg/kg over 30 min every 8 h

Locations

Country	Name	City	State
France	Chu Reims	France	Reims

Sponsors (1)

Lead Sponsor	Collaborator
CHU de Reims

Country where clinical trial is conducted

France, 

References & Publications (1)

Cousson J, Floch T, Guillard T, Vernet V, Raclot P, Wolak-Thierry A, Jolly D. Lung concentrations of ceftazidime administered by continuous versus intermittent infusion in patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2015 Ap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lung tissue concentration of ceftazidime		up to 44 hours	Yes