Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

Ventilator Associated Pneumonia Clinical Trial

— IMPACT  

Official title:

Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00950222
• Other study ID #: P061014
• Secondary ID: CRC06049
• Status: Completed
• Phase: N/A
• First received: July 28, 2009
• Last updated: July 25, 2012
• Start date: June 2009
• Est. completion date: January 2012

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The study is a prospective open trial conducted in 4 centers, and designed to determine if pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with amikacin as empirical therapy, impact microbiological and clinical outcome of patients with Gram negative bacilli (GNB) ventilator-associated pneumonia (VAP).

Description:

Inappropriate initial antibiotherapy increases mortality of many serious infections. This is the case for ventilator-associated pneumonia, frequently occurring during intensive care unit (ICU) hospitalization, and whose 48 first hours of treatment are decisive.

It is well established that pharmacokinetic and pharmacodynamic parameters of antibiotics are correlated with their clinical and microbiological effectiveness. However in ICU patients, pharmacokinetic parameters of antibiotics suffer great variations, and bacteria responsible for these infections are usually less sensitive to antibiotics, especially Gram negative bacilli (GNB). An important pharmacodynamic variability may occur at the initial phase of the antibiotic treatment, decisive for the infection's outcome.

We propose to evaluate the correlation between pharmacokinetic and pharmacodynamic profile of the empirical antibiotic therapy and the microbiological and clinical outcome of VAP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: January 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Mechanical ventilation for more than 48 hours

3. Clinical suspicion of VAP defined by a new persistent radiological infiltrate and one of the following signs: purulent tracheal aspirations, or temperature of 38°3 or higher, or leucocyte count > 10000/ml

4. Risk of multi resistant bacteria defined as follows: at least 6 days of mechanical ventilation or antibiotic treatment in the 15 previous days

5. Distal pulmonary secretion sample obtained beforehand for microbiological diagnosis by bronchoalveolar lavage via bronchoscopy or blinded protected telescoping catheter via bronchoscopy or blindly

6. Presence of GNB on direct examination of the distal pulmonary secretion sample

7. Realization of a preliminary medical examination. 8- Written inform consent from the patient or relatives. The consent may be obtained after the enrollment if the patient is not able to give consent and if there is no relatives

Exclusion Criteria:

1. Time between distal pulmonary secretion sample taking and the 1st administration of imipenem exceeding 24 hours

2. Pregnancy

3. Severely impaired renal function (creatinine clearance lower than 10 mL/mn or renal replacement therapy)

4. Allergy to imipenem or amikacin

5. Treatment in progress with imipenem or amikacin

6. Death expected within 48 hours following diagnosis of VAP

7. Myasthenia

8. Simultaneous administration of others aminoglycosides

9. Association with intravenous polymyxin or botulinum toxin

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Imipenem/Amikacin
patients will received as empirical therapy for VAP imipenem associated with amikacin.

Locations

Country	Name	City	State
France	Victor Dupouy Hospital	Argenteuil

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	Variation of numeration (cfu per ml) of GNB, for whom culture of pulmonary samples are positive (higher than defined thresholds), between the quantitative endotracheal aspiration (QAE) obtained at H0 (initiation of treatment) and QAE obtained at H48		Hour 48	No
Secondary	To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP		Hour 24	No
Secondary	To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP		Hour 24	No
Secondary	To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved		Hour 24	No
Secondary	To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP		Hour 24	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3		Day 3	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters variability on the CPIS, clinical score of VAP, measured 48 hours after initiation of the treatment		Hour 48	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6		Day 8	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment		Day 8	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters on serum procalcitonin levels evolution between the initiation of the treatment and 48 hours after the initiation of the treatment of the VAP		Hour 48	No
Secondary	To assess the impact of imipenem and amikacin PK/PD parameters on mortality at day 28 (Day 28) 11- to assess the impact of imipenem and amikacin PK/PD parameters on VAP relapse		Day 28	No
Secondary	To study emergence of less sensitive bacteria to imipenem and/or amikacin, 48 hours after the initiation of the antibiotic treatment, among GNB isolated in endotracheal aspiration before initiation of this treatment		Hour 48	No
Secondary	To study emergence in the tracheal and digestive flora of micro-organisms resistant to imipenem after the first 48 hours of treatment by imipenem		Hour 48	No