Lung Concentrations of Ceftazidime in Patients With Ventilator-associated Pneumonia (CEFTALC)

• ClinicalTrials.gov Identifier: NCT02837835
• Recruitment Status: Completed
• First Posted: July 20, 2016
• Last Update Posted: July 20, 2016
• Sponsor: CHU de Reims
• Information provided by (Responsible Party): CHU de Reims

Tracking Information

• First Submitted Date: July 13, 2016
• First Posted Date: July 20, 2016
• Last Update Posted Date: July 20, 2016
• Study Start Date: March 2005
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 15, 2016): lung tissue concentration of ceftazidime [ Time Frame: up to 44 hours ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lung Concentrations of Ceftazidime in Patients With Ventilator-associated Pneumonia
• Official Title: Comparison of Lung Concentrations of Ceftazidime Administered by Continuous Versus Intermittent Infusion in Patients With Ventilator-associated Pneumonia
• Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pneumonia

Intervention

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

Study Arms

• Experimental: continuous administration of ceftazidime
  Intervention: Drug: ceftazidime
• Experimental: intermittent administration of ceftazidime
  Intervention: Drug: ceftazidime

• Publications *: 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 Apr;59(4):1905-9. doi: 10.1128/AAC.04232-14. Epub 2015 Jan 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2016): 34
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: February 2008
• Actual Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02837835
• Other Study ID Numbers: 104R04
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: CHU de Reims
• Study Sponsor: CHU de Reims
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: CHU de Reims
• Verification Date: July 2016