The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia

November 24, 2015 updated by: Sutep Jaruratanasirikul

The study was a randomized three-way crossover study. Each subject received meropenem in three regimens at room temperature consecutively: (i) bolus injection of 1 g of meropenem over 10 min every 8 h for 24 h, (ii) 3-h infusion of 1 g of meropenem via an infusion pump at a constant flow rate every 8 h for 24 h, and(iii) 3-h infusion of 2 g of meropenem via an infusion pump at a constant flow rate every 8 h for 24 h.

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

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

Meropenem pharmacokinetic studies were carried out during administration of the third dose of each regimen (16 to 24 h after the start of each regimen). Blood samples (approximately 5 ml) were obtained by direct venipuncture at the following times: before (time zero) and 10 and 30 min and

1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the third dose of each regimen.

The concentrations of meropenem were determined by reverse-phase high-performance liquid chromatography.

Concentration of meropenem 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 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:

Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity against several pathogens. In common with other -lactams, the main pharmacokinetic/pharmacodynamic parameter that correlates with the therapeutic efficacy is the T>MIC, and administration by continuous infusion is the preferred route to maximize this parameter. However, in tropical countries the stability of meropenem is an important consideration when continuous infusion is to be used.

Objective:

The aim of this study was to demonstrate the T>MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection.

Study design:

The study was conducted with nine patients with ventilator-associated pneumonia. Each subject received meropenem in three regimens consecutively: (i) bolus injection of 1 g every 8 h for 24 h; (ii) 3-h infusion of 1 g every 8 h for 24 h; and (iii) 3-h infusion of 2 g every 8 h for 24 h.

Sample collections:

Meropenem pharmacokinetic studies were carried out during administration of the third dose of each regimen (16 to 24 h after the start of each regimen). Blood samples (approximately 5 ml) were obtained by direct venipuncture at the following times: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the third dose of each regimen.

Meropenem assay:

The concentrations of meropenem were determined by reverse-phase high-performance liquid chromatography. Cefepime (100 mcg/ml) was used as the internal standard, and the samples were extracted by the method of Ozkan et al.

Clinical data and pathogens collection:

  1. Initial patient demographic data (age, sex, weight, diagnosis, APACHE II scores) will be collected upon enrollment in the study.
  2. The Gram negative bacilli isolated from sputum in 9 patients will be collected and the MIC of the meropenem for pathogens will be determined by E tests upon enrollment in the study.

Duration of study:

Patients will receive meropenem for 3 days

Pharmacokinetic and pharmacodynamic analysis:

Concentration of meropenem 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 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
      • Hatyai, 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:

  • The patients were eligible for the study if they met the following criteria:

    1. older than 18 years
    2. clinical suspicion of VAP, 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 celsius or higher, or a leukocyte count higher than 10000.

Exclusion Criteria:

  • Patients were excluded from the study if they were pregnant or in circulatory shock (which was defined as a systolic blood pressure of 90 mmHg and poor tissue perfusion) or had documented hypersensitivity to meropenem or an estimated creatinine clearance(determined by the Cockcroft-Gault method) of 60 ml/min.

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: Parallel 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: 1 g by bolus injection
1 g of meropenem with bolus injection every 8 h regimen
Drug: Meropenem
1 g in 100 ml of normal saline solution and administered via bolus injection Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 hh after 3rd dose of meropenem
Other Names:
  • Meronem
Drug: Meropenem

1 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and

1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem
Drug: Meropenem

2 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem
Experimental: 1 g by 3 h infusion
1 g of meropenem with 3 h infusion every 8 h regimen
Drug: Meropenem
1 g in 100 ml of normal saline solution and administered via bolus injection Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 hh after 3rd dose of meropenem
Other Names:
  • Meronem
Drug: Meropenem

1 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and

1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem
Drug: Meropenem

2 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem
Experimental: 2 g by 3 hinfusion
2 g of meropenem with 3 h infusion every 8 h regimen
Drug: Meropenem
1 g in 100 ml of normal saline solution and administered via bolus injection Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 hh after 3rd dose of meropenem
Other Names:
  • Meronem
Drug: Meropenem

1 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and

1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem
Drug: Meropenem

2 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 3 h every 8 h.

Blood samples (approximately 5 ml)will be obtained by direct venepuncture at the following time: before (time zero) and 10 and 30 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the 3rd dose of meropenem.

Other Names:
  • Meronem

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
Concentration of meropenem in plasma
Time Frame: 8 hours profile after 3rd dose of meropenem
Concentration of doripenem 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 Faction Response).
8 hours profile after 3rd dose of meropenem

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

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sutep Jaruratanasirikul, MD, 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, 2004

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, 2005

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, 2005

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 24, 2015

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.
November 24, 2015

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.
November 25, 2015

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.
November 25, 2015

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.
November 24, 2015

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.
November 1, 2015

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.
  • MR-13/2545

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.

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