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

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

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

Study Overview

• Status: Recruiting
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Continuous infusion Linezolid; Drug: intermittent dosing linezolid

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.

• Study Type: Interventional
• Enrollment (Anticipated): 169
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rania M Sarhan, PhD; Phone Number: 0021008789509

Study Locations

• Egypt
  • Banī Suwayf, Egypt
    • Recruiting
    • Beni-Suef University
    • Principal Investigator: Rania M Soliman, Ph.D
    • Principal Investigator: Ayman N Moharram, MD
    • Principal Investigator: Heba Farouk, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Continuous infusion; 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; Linezolid 600 mg intravenous Loading dose followed by 1200 mg/ day by Continuous infusion ( 50 mg /hr ); Other Names: intervention
ACTIVE_COMPARATOR: Intermittent dosing; Patients will be received Linezolid 600 mg intravenous twice daily over 30 to 60 minutes	Drug: intermittent dosing linezolid; Linezolid 600 mg intravenous twice daily; 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

Collaborators and Investigators

• Sponsor: October 6 University
• Collaborators: Beni-Suef University
• Investigators: Principal Investigator: Ahmed Essam, BSc, October 6 University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2019
• Primary Completion (ANTICIPATED): September 15, 2021
• Study Completion (ANTICIPATED): September 15, 2021

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (ACTUAL): August 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: pneumonia; critically ill patients; linezolid continuous infusion
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: REC-H-PhBSU-20004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No