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

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

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.

Study Overview

• Status: Unknown
• Conditions: Critical Illness; Bacterial Infections
• Intervention / Treatment: Drug: Meropenem; Drug: Imipenem

• Study Type: Observational
• Enrollment (Anticipated): 102

Contacts and Locations

• Study Contact: Name: Sutep o Jaruratanasirikul, M.D.; Phone Number: 6674451485 6674451485; Email: jasutep@medicine.psu.ac.th
• Study Contact Backup: Name: Monchana o Nawakitrangsan, M.Pharm.; Phone Number: 6674451485 6674451485; Email: nana_jittung@hotmail.com

Study Locations

• Thailand
  • Songkla
    • Hat Yai, Songkla, Thailand, 90110
      • Recruiting
      • Faculty of Medicine, Prince of Songkla University, Thailand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients

Description

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

Exclusion Criteria:

• severe renal impairment and require renal replacement therapy
• APACHE II score >30
• History of hypersensitivity to carbapenems
• Pregnancy or breast-feeding female

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relationship between %fT>MIC and clinical cure	Clinical cure: disappearance of all signs and symptoms related to the infection, such that no additional antibacterial therapy, drainage, or surgical procedure was required.	Day 3-7 after treatment and end of therapy (7-14)
The relationship between %fT>MIC and microbiological cure	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).	Day 3-7 after treatment and end of therapy (7-14)
The relationship between %fT>MIC and mortality	All-cause mortality	during hospital stay and at day 28

Collaborators and Investigators

• Sponsor: Prince of Songkla University

Publications and helpful links

General Publications

• Jaruratanasirikul S, Boonpeng A, Nawakitrangsan M, Samaeng M. NONMEM population pharmacokinetics and Monte Carlo dosing simulations of imipenem in critically ill patients with life-threatening severe infections during support with or without extracorporeal membrane oxygenation in an intensive care unit. Pharmacotherapy. 2021 Jul;41(7):572-597. doi: 10.1002/phar.2597. Epub 2021 Jun 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: February 24, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (ACTUAL): February 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 1, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; meropenem; pharmacodynamics; imipenem
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Bacterial Infections and Mycoses; Critical Illness; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protease Inhibitors; Anti-Bacterial Agents; Imipenem; Cilastatin; Meropenem
• Other Study ID Numbers: B-lactams-ICU-61061141

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No