Observed Pharmacokinetic of Piperacillin/Tazobactam Compared to Amikacin in ICU (OPTIMA)

Observed Pharmacokinetic of Piperacillin/Tazobactam in ICU Patients Compared to Therapeutic Drug Monitoring of Amikacin

The pharmacokinetics of antimicrobials is profoundly modified in Intensive care unit (ICU) patients. To adapt the treatment, it is recommended to measure blood levels of antibiotics. Some antibiotics, such as amikacin, are easy to monitor, while for other molecules, such as piperacillin/tazobactam, the drug monitoring is more difficult to obtain. These two molecules have similar physicochemical characteristics (hydrophilicity) and therefore have closed pharmacokinetic properties. OPTIMA is a study aiming at criteria will be used to judge whether the pharmacokinetic (PK) parameters of amikacin are predictive of those of piperacillin and tazobactam.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Sepsis Syndrome
• Intervention / Treatment: Biological: Plasma dosage of amikacin, piperacillin and tazobactam

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arnaud FRIGGERI, MD; Phone Number: +33 478865647; Email: arnaud.friggeri@chu-lyon.fr
• Study Contact Backup: Name: Alain LEPAPE, MD; Phone Number: +33 478861989; Email: alain.lepape@chu-lyon.fr

Study Locations

• France
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Service d'Anesthésie et Réanimation - Secteur de Soins Critiques, Groupement Hospitalier Sud, HCL
    • Contact: Arnaud FRIGGERI, MD; Phone Number: +33 478865647; Email: arnaud.friggeri@chu-lyon.fr
    • Principal Investigator: Arnaud FRIGGERI, MD
    • Sub-Investigator: Alain LEPAPE, MD
    • Sub-Investigator: Bernard ALLAOUCHICHE, MD, Prof.
    • Sub-Investigator: Julien BOHE, MD, Prof.
    • Sub-Investigator: Manon MARIE, MD
    • Sub-Investigator: Florent WALLET, MD
    • Sub-Investigator: Olivia VASSAL, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient ≥ 18 years old
• Patient hospitalized in the critical care department of the Lyon-Sud hospital centre
• Patient with a sepsis or a severe sepsis table defined by the latest international recommendations
• Patient to be treated by the amikacin + piperacillin/tazobactam association
• Patient affiliated to a social security system, having agreed to participate in the study

Exclusion Criteria:

• Patient with a known history of hypersensitivity or contraindication to amikacin, piperacillin or tazobactam
• Patient known to have previously received piperacillin/tazobactam or amikacin combination before inclusion
• Patient treated at the time of inclusion with dialysis techniques

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients treated by amikacin and piperacillin; ICU patient with a sepsis treated by amikacin and piperacillin/tazobactam	Biological: Plasma dosage of amikacin, piperacillin and tazobactam; Pharmacokinetic (PK) criteria will be used to judge whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma concentration of amikacin during the first 24 hours after administration		First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma concentration of piperacillin during the first 24 hours after administration		First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma concentration of tazobactam during the first 24 hours after administration		First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Dose administered of amikacin at baseline		Hour 0 (Baseline)
Dose administered of piperacillin at baseline		Hour 0 (Baseline)
Dose administered of tazobactam at baseline		Hour 0 (Baseline)
Change in plasma volume of distribution of amikacin during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma volume of distribution of piperacillin during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma volume of distribution of tazobactam during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma volume of distribution is one of the two PK parameters evaluated in this study (with clearance), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma clearance of amikacin during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma clearance of piperacillin during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)
Change in plasma clearance of tazobactam during the first 24 hours after administration	In order to evaluate whether the PK parameters of amikacin are predictive of those of piperacillin and tazobactam. Plasma clearance is one of the two PK parameters evaluated in this study (with volume of distribution), calculated with drug plasma concentration and dose administered	First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2021
• Primary Completion (Anticipated): January 28, 2023
• Study Completion (Anticipated): January 28, 2023

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amikacin; Piperacillin; Tazobactam
• Other Study ID Numbers: 69HCL17_0843

Drug and device information, study documents

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