The Population Pharmacokinetics of Imipenem in Patients With Ventilator-associated Pneumonia

December 8, 2011 updated by: Sutep Jaruratanasirikul

This is prospective, randomized and crossover design to assess the pharmacokinetic and pharmacodynamics of three regimen.

  • 0.5-hr infusion of imipenem 0.5 g every 6 hrs
  • 2-hr infusion of imipenem 0.5 g every 6 hrs
  • 2-hr infusion of imipenem 1 g every 6 hrs

Clinical and laboratory data such as Age,Sex, Body weight, CBC, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Sample and Blood culture will be collected.

Nine patients will be enrolled in this study. After completion of the imipenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.

Blood samples (approximately 3 ml) will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 5 and 6 after 4th dose of imipenem.

Concentration of imipenem in plasma will be measured by HPLC method. Then, the data will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Introduction: Ventilator-associated pneumonia (VAP) is a common cause of nosocomial infection with a high mortality rate. In the current era of increasing highly resistant pathogens in nosocomial infections, the empirical treatment of these organisms is becoming more difficult and only a few novel antimicrobial agents are currently in development with activity against these highly resistant Gram negative bacilli infections. Imipenem, a carbapenem antibiotic, is a β-lactam antibacterial agent with a broad spectrum of activity against both Gram positive and Gram negative bacteria. This agent is still one of the most commonly used antibiotics for empirical therapy of highly resistant nosocomial infections in VAP. In common with other β-lactams, imipenem exhibits primarily time dependent killing and increasing the concentration of this agent does not necessarily increase the rate and extent of bacterial killing. Therefore, the time that concentrations in serum are above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with efficacy. Pharmacodynamic analysis can be applied to imipenem dosages to increase the likelihood of optimal exposure and achieve good clinical responses in patients with VAP. Previous studies we performed found that a 2 h infusion of carbapenem antibiotics gave greater values for T>MIC than a 0.5 h infusion. Therefore, in an attempt to improve the efficacy of the present β-lactam antimicrobial agents such as imipenem, a prolonged infusion would be the appropriate mode for administration to promote the maximal bactericidal effect.PK changes have been found for several hydrophilic antimicrobial agents in critically ill patients. Drug dispositions are altered in this patient population when compared with healthy subjects leading to fluctuations of plasma concentrations. Therefore, the aim of this study was to assess the PD of imipenem in VAP patients, comparing administration by 0.5 h infusion or 2 h infusion.

Objectives: To assess the pharmacokinetic and pharmacodynamics of three regimen as below.

i) 0.5-hr infusion of imipenem 0.5 g every 6 hrs ii) 2-hr infusion of imipenem 0.5 g every 6 hrs iii) 2-hr infusion of imipenem 1 g every 6 hrs

Drug preparation:Imipenem will be reconstituted with 100 ml saline solution according to the manufacturer's guidelines

Study design: This is prospective, randomized and crossover design to assess

Each patients will receive doripenem in 3 regimens consecutively:

i) 0.5-hr infusion of imipenem 0.5 g every 6 hrs ii) 2-hr infusion of imipenem 0.5 g every 6 hrs iii) 2-hr infusion of imipenem 1 g every 6 hrs

Nine patients will be enrolled in this study. After completion of the imipenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.

Sample collections: Blood samples (approximately 3 ml) will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 5 and 6 after 4th dose of imipenem. All blood samples will be allowed to clot and then centrifuged at 2,000g. The serum obtained will be stored at-80°C until analysis.

Imipenem assays by HPLC method e performed at Department of Medicine, Faculty of Medicine.

Clinical and laboratory data such as Age,Sex, Body weight, CBC, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Sample and Blood culture will be collected.

Duration of study: Patients will receive imipenem for 3 days

Pharmacokinetic and pharmacodynamic analysis: Concentration of imipenem in plasma will be measured by HPLC method and simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response).

Sample Size: Nine patients with VAP will be enrolled in this study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
    • Songkla
      • Hat Yai, Songkla, Thailand, 90110
        • Prince of Songkla University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged ≥ 18 years
  • Patients are intubated and receiving mechanical ventilation.
  • Patients have clinical suspicion of VAP with Gram negative bacilli infections, defined by a new and persistent infiltrate on chest radiography associated with at least one of the following: purulent tracheal secretions, temperature of 38.3°C or higher or a leucocyte count higher than 10000 cells/mm3.
  • Expected life expectancy ≥ 3 days

Exclusion Criteria:

  • Patients have documented hypersensitivity to imipenem or other carbapenems.
  • Patients have an estimated creatinine clearance < 60 ml/min
  • Patients are in circulatory shock (defined as a systolic blood pressure of < 90 mmHg).
  • Patients are pregnant.
  • Pretient receive imipenem for 2 weeks before randomization.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 0.5 g of imipenem by 0.5-hr infusion
0.5 g of imipenem every 6 hrs administrated by 0.5-hr infusion for 3 days
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 0.5-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
1 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Experimental: 0.5 g of imipenem by 2-hr infusion
0.5 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 0.5-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
1 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Experimental: 1 g of imipenem by 2-hr infusion
1 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 0.5-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
0.5 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)
Drug: Imipenem
1 g of imipenem every 6 hrs administrated by 2-hr infusion for 3 days
Other Names:
  • Imipenem (Tienam)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy of imipenem administration by a 0.5 h and 2 h infusion
Time Frame: At 0, 0.5, 1, 2, 3, 4, 5 and 6 hours after 4th dose of imipenem.
Concentration of imipenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Fraction Response).
At 0, 0.5, 1, 2, 3, 4, 5 and 6 hours after 4th dose of imipenem.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sutep Jaruratanasirikul

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Prince of Songkla University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 23, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IMI-50-372-028

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ventilator-Associated Pneumonia

Clinical Trials on Imipenem

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings