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The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia

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ClinicalTrials.gov Identifier: NCT02615041
Recruitment Status : Completed
First Posted : November 25, 2015
Last Update Posted : November 25, 2015
Sponsor:
Collaborator:
Prince of Songkla University
Information provided by (Responsible Party):
Sutep Jaruratanasirikul, Prince of Songkla University

Brief Summary:

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)


Condition or disease Intervention/treatment Phase
Ventilator-Associated Pneumonia Drug: Meropenem Phase 4

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 : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia
Study Start Date : January 2004
Actual Primary Completion Date : January 2005
Actual Study Completion Date : January 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia
Drug Information available for: Meropenem

Arm Intervention/treatment
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 Name: 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 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 Name: Meronem

Experimental: 2 g by 3 hinfusion
2 g of meropenem with 3 h infusion every 8 h regimen
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 Name: Meronem




Primary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02615041


Locations
Thailand
Prince of Songkla University
Hatyai, Songkla, Thailand, 90110
Sponsors and Collaborators
Sutep Jaruratanasirikul
Prince of Songkla University
Investigators
Principal Investigator: Sutep Jaruratanasirikul, MD Prince of Songkla University

Responsible Party: Sutep Jaruratanasirikul, Principal Investigator, Prince of Songkla University
ClinicalTrials.gov Identifier: NCT02615041     History of Changes
Other Study ID Numbers: MR-13/2545
First Posted: November 25, 2015    Key Record Dates
Last Update Posted: November 25, 2015
Last Verified: November 2015

Keywords provided by Sutep Jaruratanasirikul, Prince of Songkla University:
Meropenem
Ventilator-Associated Pneumonia
population pharmacokinetics
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:
Pneumonia, Ventilator-Associated
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Meropenem
Thienamycins
Anti-Bacterial Agents
Anti-Infective Agents