Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Ventilator Associated Pneumonia Clinical Trial

— DARTAGNAN  

Official title:

Phase II Study of High Dose Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00861315
• Other study ID #: DARTAGNAN
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: March 12, 2009
• Last updated: March 13, 2009
• Start date: January 2009
• Est. completion date: January 2011

Study information

• Verified date: March 2009
• Source: Association Pour La Promotion A Tours De La Reanimation Medicale
• Contact: Stephan Ehrmann, MD
• Phone: +33(0)671103302
• Email: stephanehrmann[@]gmail.com
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Drug:
• Nebulized amikacin
Amikacin is nebulized at a dose of 60 mg/Kg (6 first patients of the arm), 80 mg/Kg (6 subsequent patients) or 100 mg/Kg (last 6 patients of the arm)
• Intravenous amikacin
20 mg/Kg amikacin are administred intravenousely once a day during three days.
• Placebo nebulization
0.9% saline solution is nebulized once a day during three days
• Placebo infusion
0.9% saline is administered intravenousely once a day during three days

Locations

Country	Name	City	State
France	Service de réanimation médicale. Hôpital La Source. CH Orléans	Orléans	Loiret
France	Service de réanimation médicale polyvalente. Hôpital Bretonneau CHRU	Tours	Indre et Loire

Sponsors (1)

Lead Sponsor	Collaborator
Association Pour La Promotion A Tours De La Reanimation Medicale

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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			Yes
Secondary	Comparison of clinical pulmonary infection score evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin		10 days	No
Secondary	Comparison of serum procalcitonin concentration evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin		10 days	No
Secondary	Comparison of c reactive protein evolution between patients treated with nebulized amikacin and patients treated with intravenous amikacin		10 days	No
Secondary	Comparison duration of mechanical ventilation between patients treated with nebulized amikacin and patients treated with intravenous amikacin		10 days	No