PK/PD and Clinial Outcomes of Beta-lactams in ICU Patients

Sponsor

Prince of Songkla University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03858387

Collaborator

(none)

102

Enrollment

Location

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Meropenem and imipenem are broad-spectrum carbapenem antibiotic and are frequently prescribed in critically ill patients with severe infections. These patients show several pathophysiological changes that may alter the carbapenem pharmacokinetic (PK) normally found in other populations. Although the PK of carbapenems has been widely studied, most studies have been conducted on small populations, and clinical outcome data are sparse. Therefore, the aims of this study are (i) describe the population pharmacokinetic parameters of meropenem and imipenem in critically ill subject (ii) evaluate the pharmacodynamic of meropenem and imipenem as a predictor of clinical treatment outcome.

Condition or Disease	Intervention/Treatment	Phase
Critical Illness Bacterial Infections	Drug: Meropenem Drug: Imipenem

Study Design

Study Type:

Observational

Anticipated Enrollment :

102 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Pharmacokinetics/Pharmacodynamics and Clinical Outcomes of β-lactams in Critically Ill Patients

Actual Study Start Date :

Sep 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Meropenem Critically ill patients who require meropenem therapy	Drug: Meropenem This group is composed of 52 critically ill patients, meropenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2.5 h, 2.5-4 h, 4-8 h or 4-12 after meropenem administration.
Imipenem Critically ill patients who require imipenem therapy	Drug: Imipenem This group is composed of 50 critically ill patients, imipenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2 h, 2-4 h, 4-6 h or 4-12 after imipenem administration. Other Names: Imipenem/cilastatin

Arm

Intervention/Treatment

Meropenem

Critically ill patients who require meropenem therapy

Drug: Meropenem

This group is composed of 52 critically ill patients, meropenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2.5 h, 2.5-4 h, 4-8 h or 4-12 after meropenem administration.

Imipenem

Critically ill patients who require imipenem therapy

Drug: Imipenem

This group is composed of 50 critically ill patients, imipenem dosage is chosen by the intensivist in charge of the case. Blood sampling: 5 blood samples (3 mL) were obtained from a heparinized intravascular catheter by direct venipuncture at the following time: before (time 0) and during 0-0.5 h, 0.5-2 h, 2-4 h, 4-6 h or 4-12 after imipenem administration.

Other Names:

Imipenem/cilastatin

Outcome Measures

Primary Outcome Measures

Population pharmacokinetic parameters of meropenem and imipenem [24-48 hours after treatment]
%fT>MIC of meropenem and imipenem [24-48 hours after treatment]
the percentage of time which the free drug concentration remains above the minimum inbibitory concentration (%fT>MIC)

Secondary Outcome Measures

The relationship between %fT>MIC and clinical cure [Day 3-7 after treatment and end of therapy (7-14)]
Clinical cure: disappearance of all signs and symptoms related to the infection, such that no additional antibacterial therapy, drainage, or surgical procedure was required.
The relationship between %fT>MIC and microbiological cure [Day 3-7 after treatment and end of therapy (7-14)]
Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure).
The relationship between %fT>MIC and mortality [during hospital stay and at day 28]
All-cause mortality

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age >18 years
severely ill patient who admitted to medical or surgical intensive care unit who require a treatment with meropenem or imipenem antibiotic