Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care

Ventilator-associated Pneumonia Clinical Trial

— TARGET-REA  

Official title:

Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care: Pharmacodynamic Evaluation and Impact.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02127528
• Other study ID #: P1101137
• Status: Recruiting
• Phase: N/A
• First received: November 7, 2013
• Last updated: April 15, 2016
• Start date: May 2014
• Est. completion date: December 2016

Study information

• Verified date: April 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Olivier Pajot, MD
• Phone: +33 1 34 23 24 51
• Email: olivier.pajot[@]ch-argenteuil.fr
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

this study aims to verify the adequacy of doses of antibiotics prescribed in clinical practice for the treatment of ventilated acquired pneumonia (VAP) in the intensive care unit (ICU) with the pharmacodynamic efficacy criteria considered relevant literature. The impact of these pharmacodynamic parameters on the clinical and microbiological VAP will be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Use of mechanical ventilation for more than 48 hours

2. Clinical suspicion of ventilation-acquired pneumonia (VAP) defined by new radiological persisting infiltrate (or ARDS) AND one of the following features:

purulent tracheal aspirates OR temperature = 38.3°C OR leukocytosis> 10 giga/L

3. High risk of multidrug-resistant bacteria, defined as either at least 6 days of mechanical ventilation OR antibiotic treatment in the previous 15 days

4. Implementation of a prior distal respiratory sample for microbiological diagnosis by bronchoalveolar lavage (BAL) OR distal sampling by protected catheter (PDP)

5. Age = 18 years

6. Implementing a medical examination

7. Obtain the written consent of the patient, one of its relatives or trusted person previously designated or emergency clause.

Exclusion Criteria:

1. Pregnant woman

2. Expected death within 72 hours of diagnosis of VAP patient

3. Dialysis

4. No affiliation to a social security scheme (beneficiary or legal)

5. Contraindication to one of classes of molecules used antibiotics (ß-lactam / Fluoroquinolones / Aminoglycosides), contained in the Summary of Product Characteristics for authorization on the market.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator-associated Pneumonia

Locations

Country	Name	City	State
France	CH Victor Dupouy	Argenteuil	Val d'Oise

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	adequate antibiotics	proportion of patients for whom the pharmacodynamic target defined a priori according to data from the literature is reached for each antibiotic anti Gram-negative bacillus used empirically activity (including ß-lactams, fluoroquinolones and aminoglycosides)	28 days	No
Secondary	Bacterial species	Bacterial species in question, defined as any bacteria isolated in significant amounts on the diagnostic breath sampling	28 days	No
Secondary	Distribution of the main pharmacodynamic parameters	ratio of the peak serum level (Cmax) on the minimal inhibitory concentration (MIC), ie Cmax/MIC ratio (for aminoglycosides and fluoroquinolones): distribution in the population and proportion of patients with Cmax/MIC> 10; ratio of the Area Under the serum concentration time Curve (AUC) on the MIC, ie AUC/MIC ratio (for fluoroquinolones) : distribution in the population and proportion of patients with an AUC/MIC ratio> 125; percentage of time spent above the MIC between 2 injections, and trough/MIC ratio (for ß-lactams): distribution in the population and proportion of patients with a T>MIC of 100% (intermittent infusion) or trough/MIC> 4 (continuous infusion)	28 days	No
Secondary	Eradication of gram negative bacilli responsible for VAP	defined as a bacterial count from distal respiratory sample realized during the third day of treatment, less than the threshold for each isolated Gram negative bacilli initially beyond these thresholds	28 days	No
Secondary	Death		28 days	Yes
Secondary	Number of days alive without mechanical ventilation		28 days	Yes
Secondary	Clinical recovery	defined as patient alive with Clinical Pulmonary Infection Score (CPIS) <8	28 days	No
Secondary	Score of organ failure (SOFA)	repeated measures every 48h for 8 days	8 days	No