Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic (IMPACT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00950222
First received: July 28, 2009
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

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).


Condition Intervention
Ventilator Associated Pneumonia
Drug: Imipenem/Amikacin

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

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 [ Time Frame: Hour 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP [ Time Frame: Hour 24 ] [ Designated as safety issue: No ]
  • To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP [ Time Frame: Hour 24 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP [ Time Frame: Hour 24 ] [ Designated as safety issue: No ]
  • To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3 [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 70
Study Start Date: June 2009
Study Completion Date: January 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1:Imipenem/Amikacin

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

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950222

Locations
France
Victor Dupouy Hospital
Argenteuil, France, 95100
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Olivier PAJOT, MD HOPITAL ARGENTEUIL
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00950222     History of Changes
Other Study ID Numbers: P061014, CRC06049
Study First Received: July 28, 2009
Last Updated: July 25, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Intensive care unit
Ventilator associated pneumonia
Gram negative bacilli infection
Empirical antibiotic therapy
Pharmacokinetic / pharmacodynamic
Imipenem
Amikacin
Gram negative bacilli

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Amikacin
Imipenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014