Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic

NCT00950222 | Completed

• 2 other identifiers: P061014CRC06049
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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).

Conditions

Ventilator Associated Pneumonia

Keywords

Intensive care unit; Ventilator associated pneumonia; Gram negative bacilli infection; Empirical antibiotic therapy; Pharmacokinetic / pharmacodynamic; Imipenem; Amikacin; Gram negative bacilli

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP

  Hour 24

• To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP

  Hour 24

• To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved

  Hour 24

• To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP

  Hour 24

• To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3

  Day 3

Study Arms (1)

1:Imipenem/Amikacin

EXPERIMENTAL

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

Interventions

Imipenem/Amikacin DRUG

patients will received as empirical therapy for VAP imipenem associated with amikacin.

Also known as: Therapy for VAP imipenem associated with amikacin

1:Imipenem/Amikacin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Victor Dupouy Hospital

Argenteuil, 95100, France

Location

Related Publications (2)

• 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.

  PMID: 25327505 DERIVED

• 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.

  PMID: 24903189 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Gram-Negative Bacterial Infections

Interventions

Imipenem; Amikacin; Therapeutics

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Olivier PAJOT, MD

  HOPITAL ARGENTEUIL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 31, 2009
• Study Start: June 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: January 1, 2012
• Last Updated: July 26, 2012

Record last verified: 2012-07

Locations

FR (1)