Clinical trial NCT00861315: Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation
Official title: Phase II Study of High Dose Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Ventilator Associated Pneumonia
Keywords: Pneumonia
Nebulization
Amikacin
Lead sponsor: Association Pour La Promotion A Tours De La Reanimation Medicale
Sponsor class: OTHER
First posted: 2009-03-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determintion of nebulized amikacin dose (60 mg/Kg, 80 mg/Kg or 100 mg/Kg) which results in serum amikacin concentrations equal or below the serum amikacin concentrations measured after 20 mg/Kg intravenous amikacin infusion
Secondary outcomes:
measure: Comparison of clinical pulmonary infection score evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin
timeFrame: 10 days
measure: Comparison of serum procalcitonin concentration evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin
timeFrame: 10 days
measure: Comparison of c reactive protein evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin
timeFrame: 10 days
measure: Comparison duration of mechanical ventilation between patients treated with nebulized amikacin and patients treated with intravenous amikacin
timeFrame: 10 days
Other outcomes:
Locations:
city: Tours
country: France
facility: Service de réanimation médicale polyvalente. Hôpital Bretonneau CHRU
state: Indre et Loire
city: Orléans
country: France
facility: Service de réanimation médicale. Hôpital La Source. CH Orléans
state: Loiret
Study officials:
References: