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Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic (IMPACT)

Primary Purpose

Ventilator Associated Pneumonia

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Imipenem/Amikacin
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ventilator Associated Pneumonia focused on measuring Intensive care unit, Ventilator associated pneumonia, Gram negative bacilli infection, Empirical antibiotic therapy, Pharmacokinetic / pharmacodynamic, Imipenem, Amikacin, Gram negative bacilli

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Victor Dupouy Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1:Imipenem/Amikacin

Arm Description

patients will receive as empirical therapy for VAP imipenem associated with amikacin.After primary outcome measure, antibiotic therapy will be left at the discretion of the physician in charge of the patient. Imipenem: recommended usual dosage for VAP treatment, IV (in the vein), every 8 hours Amikacin: recommended usual dosage for VAP treatment (20mg/kg), IV (in the vein), single dose (at H0) for the 48 first hours of treatment

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP
To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP
To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved
To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP
To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3
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
To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6
To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment
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
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
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
To study emergence in the tracheal and digestive flora of micro-organisms resistant to imipenem after the first 48 hours of treatment by imipenem

Full Information

First Posted
July 28, 2009
Last Updated
July 25, 2012
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00950222
Brief Title
Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic
Acronym
IMPACT
Official Title
Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ventilator Associated Pneumonia
Keywords
Intensive care unit, Ventilator associated pneumonia, Gram negative bacilli infection, Empirical antibiotic therapy, Pharmacokinetic / pharmacodynamic, Imipenem, Amikacin, Gram negative bacilli

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1:Imipenem/Amikacin
Arm Type
Experimental
Arm Description
patients will receive as empirical therapy for VAP imipenem associated with amikacin.After primary outcome measure, antibiotic therapy will be left at the discretion of the physician in charge of the patient. Imipenem: recommended usual dosage for VAP treatment, IV (in the vein), every 8 hours Amikacin: recommended usual dosage for VAP treatment (20mg/kg), IV (in the vein), single dose (at H0) for the 48 first hours of treatment
Intervention Type
Drug
Intervention Name(s)
Imipenem/Amikacin
Other Intervention Name(s)
Therapy for VAP imipenem associated with amikacin
Intervention Description
patients will received as empirical therapy for VAP imipenem associated with amikacin.
Primary Outcome Measure Information:
Title
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
Time Frame
Hour 48
Secondary Outcome Measure Information:
Title
To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP
Time Frame
Hour 24
Title
To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP
Time Frame
Hour 24
Title
To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved
Time Frame
Hour 24
Title
To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP
Time Frame
Hour 24
Title
To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3
Time Frame
Day 3
Title
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
Time Frame
Hour 48
Title
To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6
Time Frame
Day 8
Title
To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment
Time Frame
Day 8
Title
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
Time Frame
Hour 48
Title
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
Time Frame
Day 28
Title
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
Time Frame
Hour 48
Title
To study emergence in the tracheal and digestive flora of micro-organisms resistant to imipenem after the first 48 hours of treatment by imipenem
Time Frame
Hour 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Mechanical ventilation for more than 48 hours 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 Risk of multi resistant bacteria defined as follows: at least 6 days of mechanical ventilation or antibiotic treatment in the 15 previous days Distal pulmonary secretion sample obtained beforehand for microbiological diagnosis by bronchoalveolar lavage via bronchoscopy or blinded protected telescoping catheter via bronchoscopy or blindly Presence of GNB on direct examination of the distal pulmonary secretion sample 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: Time between distal pulmonary secretion sample taking and the 1st administration of imipenem exceeding 24 hours Pregnancy Severely impaired renal function (creatinine clearance lower than 10 mL/mn or renal replacement therapy) Allergy to imipenem or amikacin Treatment in progress with imipenem or amikacin Death expected within 48 hours following diagnosis of VAP Myasthenia Simultaneous administration of others aminoglycosides Association with intravenous polymyxin or botulinum toxin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier PAJOT, MD
Organizational Affiliation
HOPITAL ARGENTEUIL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Victor Dupouy Hospital
City
Argenteuil
ZIP/Postal Code
95100
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25327505
Citation
Burdet C, Pajot O, Couffignal C, Armand-Lefevre L, Foucrier A, Laouenan C, Wolff M, Massias L, Mentre F. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol. 2015 Jan;71(1):75-83. doi: 10.1007/s00228-014-1766-y. Epub 2014 Oct 21.
Results Reference
derived
PubMed Identifier
24903189
Citation
Couffignal C, Pajot O, Laouenan C, Burdet C, Foucrier A, Wolff M, Armand-Lefevre L, Mentre F, Massias L. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens. Br J Clin Pharmacol. 2014 Nov;78(5):1022-34. doi: 10.1111/bcp.12435.
Results Reference
derived

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Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

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