Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation (DARTAGNAN)

Association Pour La Promotion A Tours De La Reanimation Medicale

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Ventilator Associated Pneumonia

Treatments: Drug: Nebulized amikacin; Drug: Placebo nebulization; Drug: Placebo infusion; Drug: Intravenous amikacin

Study type: Interventional

Funder types: Other

Identifiers

NCT00861315

DARTAGNAN

Details and patient eligibility

About

Inclusion of patients undergoing mechanical ventilation and presenting a pneumonia in order to determine serum pharmacokinetics of nebulized amikacin. The primary aim is to determine the dose of amikacin to be nebulized in order to observe amikacin serum concentrations close to but inferior to those observed after standart intravenous amikacin infusion.

Full description

After inclusion, patients undergo intravenous infusion of 20 mg/Kg of amikacin with amikacin serum concentrations being monitored over the following 24 hours.

Randomization occures after this first amikacin infusion. Patients are randomized to group nebulized amikacin or intravenous amikacin. The three next days of the study patients recieve nebulized amikacin (or nebulized placebo) during mechanical ventilation and a placebo infusion (amikacin infusion in case of placebo nebulization) using a air driven jet nebulizer. Amikacin serum concentrations are monitored over 24 hours after each nebulization.

Patients are followed up during 10 days for safety and efficacy. The dose of amikacin to be nebulized is 60 mg/Kg for the first 6 patients (phase A), 80 mg/Kg for the next 6 patients (phase B) and 100 mg/Kg for the last 6 patients (phase C). Each phase is started after review of the results of the preceeding phase by an idependent safety and monitoring board.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients admitted to intensive care unit.
• Patients undergoing mechanical ventilation for more than 48H.
• Suspicion of ventilator associated pneumonia.

Exclusion criteria

• Allergy to amikacin or any compound of the medication.
• Body mass index > 30 kg/m2.
• Myasthenia gravis.
• Acute or chronic renal failure.
• Vestibulo-cochlear disease.
• Pregnancy.
• Brain death.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups

Nebulized amikacin

Experimental group

Description:

Patients receive nebulized amikacin once a day during three days. Placebo is administered intravenousely

Treatment:

Drug: Nebulized amikacin

Drug: Placebo infusion

Intravenous amikacin

Active Comparator group

Treatment:

Drug: Intravenous amikacin

Drug: Placebo nebulization