Clinical trial NCT02615041: The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia
Official title: The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ventilator-Associated Pneumonia
Keywords: Meropenem
Ventilator-Associated Pneumonia
population pharmacokinetics
pharmacokinetics
pharmacodynamics
Lead sponsor: Prince of Songkla University
Sponsor class: OTHER
Collaborators: name: Prince of Songkla University
First posted: 2015-11-25
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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)

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.

Eligibility 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.

Primary outcomes:
measure: Concentration of meropenem in plasma
timeFrame: 8 hours profile after 3rd dose of meropenem
Secondary outcomes:
Other outcomes:
Locations:
city: Hatyai
country: Thailand
facility: Prince of Songkla University
state: Songkla
Study officials:
affiliation: Prince of Songkla University
name: Sutep Jaruratanasirikul, MD
role: PRINCIPAL_INVESTIGATOR
References: