Pharmacodynamics Study of Imipenem in Patients With Ventilator Associated Pneumonia

The Pharmacodynamics of Imipenem in Critically Ill Patients With Ventilator-associated Pneumonia Following Administration by 4 h or 0.5 h Infusion

Imipenem is a carbapenem antibacterial agent with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. This agent is often used as the last line of therapy for highly resistant Gram negative bacilli nosocomial infections. In common with other beta-lactamase inhibitor, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with the therapeutic efficacy is the time that concentrations in the tissue and serum are above the MIC and administration by continuous infusion is the preferred mode of administration to maximize this parameter.

However, in tropical countries, the stability of carbapenem antibiotics is an important consideration when considering continuous infusion. Therefore, prolonged infusion may be a useful mode of administration to maximize bactericidal activity. This study will demonstrate the stability of imipenem in clinical use at room temperature in tropical countries.

Study Overview

• Status: Completed
• Conditions: Ventilator Associated Pneumonia
• Intervention / Treatment: Drug: Imipenem; Drug: Imipenem

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Songkla
    • Hat Yai, Songkla, Thailand, 90110
      • Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine, Prince of Songkla University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged > or = 20 years
• Patients who have VAP with Gram negative bacilli infections which are sensitive to imipenem by the disk diffusion

Exclusion Criteria:

• Patients who have documented hypersensitivity to imipenem or other carbapenems
• Patients who have an estimated creatinine clearance of < or = 60 ml/min
• Patients who are in circulatory shock
• Patients who are pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional arm; Infusion of 0.5 g of imipenem for 0.5 hr every 6 hr for 3-5 days	Drug: Imipenem; Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 0.5 hr infusion of 0.5 g every 6 hr of imipenem at room temperature; Other Names: Tienam; Drug: Imipenem; Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 4 hr infusion of 1 g every 8 hr of imipenem at room temperature; Other Names: Tienam
Experimental: Extended infusion arm; Infusion of 1 g of imipenem for 4 hr every 8 hr for 3-5 days	Drug: Imipenem; Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 0.5 hr infusion of 0.5 g every 6 hr of imipenem at room temperature; Other Names: Tienam; Drug: Imipenem; Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 4 hr infusion of 1 g every 8 hr of imipenem at room temperature; Other Names: Tienam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accessed PK/PD parameters	- To determine plasma Imipenem PK/PD parameters (the PK/PD index (T>MIC), the probability of target attainment (PTA) at 40% (T>MIC), the cumulative fraction of response (CFR))after 4 hr infusion of 1 gm every 8 hr compared to 0.5 hr infusion of 0.5 gm every 6 hr. Conventional arm: after first dose, blood samples will be obtained by direct venepuncture at: time 0, 0.5, 6, 6.5, 12, 12.5, 18, 18.25, 18.5, 18.75, 20, 21, 22 and 24 hr Extended infusion arm: after first dose, blood samples will be obtained by direct venepuncture at: time 0, 4, 8, 12, 16, 16.5, 17, 18, 20, 20.5, 21, 22, and 24 hr	24 hours profile after first dose of trail drug.

Collaborators and Investigators

• Sponsor: Prince of Songkla University
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 5, 2011
• First Submitted That Met QC Criteria: June 21, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Patients with ventilator-associated pneumonia
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Anti-Infective Agents; Anti-Bacterial Agents; Imipenem
• Other Study ID Numbers: MISP 39337