Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic (IMPACT)
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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 |
- 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 ]
- 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 |
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
Contacts and Locations 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 May 22, 2013