Continuous Infusion of Linezolid Versus Intermittent Dosing in the Treatment of Nosocomial Pneumonia

Study Overview
=================
Brief Summary
-----------------
The investigator's goal in this study is to determine the clinical efficacy and safety of continuous infusion in comparison with standard intermittent infusion.

Detailed Description
-----------------
Prospective randomized controlled clinical trial on critically ill Pneumonic patients, included two groups, over one year period. The first group will be administered intravenous (IV) linezolid 600mg twice daily. The second group will be prescribed linezolid (IV) 600 mg loading dose followed by 1200 mg by continuous infusion. Both groups will be co-administered intravenous (IV) Meropenem 1g every 8 hours empirically.

Official Title
-----------------
Efficacy and Safety of Continuous Infusion of Linezolid Compared With Intermittent Dosing in Critically Ill Pneumonic Patients

Conditions
-----------------
Pneumonia

Intervention / Treatment
-----------------
* Drug: Continuous infusion Linezolid
* Drug: intermittent dosing linezolid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients admitted to ICUs diagnosed as HAP or VAP Chest X-ray/ computed tomography showing new or progressive infiltrate. New onset of purulent sputum or change in sputum character. Body temperature greater than 38 ℃ or less than 35.5℃. White blood cell counts greater than 10000 /mm3 or less than 4000 /mm3. Significant quantitative pathogen cultures from respiratory secretions. Exclusion Criteria: Age <18 years, Pregnancy, Lactation Previous known allergic reaction to linezolid Creatinine Clearance (CrCl) <10 mL/min, calculated according to the Cockcroft-Gault formula Thrombocytopenia (platelet count less than 80,000/mm3) Severe hepatic failure (Child-Pugh C) Concomitant treatment with other drugs that can potentially interfere with Linezolid (i.e., macrolides, serotonin modulators, omeprazole) Acute DIC score > 4 points or hematological disorder Concurrent drug-associated Thrombocytopenia

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous infusion<br>Patients will be received linezolid 600 mg intravenous Loading dose over 30 to 60 minutes followed by 1200 mg/ day by Continuous infusion (50 mg /hr) | Drug: Continuous infusion Linezolid<br>* Linezolid 600 mg intravenous Loading dose followed by 1200 mg/ day by Continuous infusion ( 50 mg /hr )<br>* Other names: intervention;|
| Active Comparator: Intermittent dosing<br>Patients will be received Linezolid 600 mg intravenous twice daily over 30 to 60 minutes | Drug: intermittent dosing linezolid<br>* Linezolid 600 mg intravenous twice daily<br>* Other names: control;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of cured patients in the linezolid continuous infusion group versus the proportion of cured patients in the intermittent group | The primary efficacy endpoint will be evaluated as clinical cure on day 7 of Linezolid initiation. Clinical cure defined by normalized body temperature, TLC less than 10,000/mL, absence of purulent secretions, and improvement of radiological findings (x-ray), in addition to Pao2/Fio2 greater than 250 in patients. | through study completion, over one year | 
| Percentage of occurrence of anemia and thrombocytopenia | The patients' hematological parameters (hemoglobin (Hb), hematocrit (Hct), and platelets (PLTs) counts) will be compared every 2 days during linezolid treatment between two groups. Anemia is defined as decrease in hemoglobin level <10 g/dl and Thrombocytopenia is defined as decrese in platelets count <100 × 103/mm3 | through study completion, over one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
linezolid continuous infusion, pneumonia, critically ill patients