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

• ClinicalTrials.gov Identifier: NCT03990467
• Recruitment Status: Recruiting
• First Posted: June 19, 2019
• Last Update Posted: September 30, 2022
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Septic Shock; Sepsis; Sepsis Syndrome	Biological: Plasma dosage of amikacin, piperacillin and tazobactam	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Observed Pharmacokinetic of Piperacillin/Tazobactam in ICU Patients Compared to Therapeutic Drug Monitoring of Amikacin
• Actual Study Start Date: January 28, 2021
• Estimated Primary Completion Date: January 28, 2023
• Estimated Study Completion Date: January 28, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in plasma concentration of amikacin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]
2. Change in plasma concentration of piperacillin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]
3. Change in plasma concentration of tazobactam during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]
4. Dose administered of amikacin at baseline [ Time Frame: Hour 0 (Baseline) ]
5. Dose administered of piperacillin at baseline [ Time Frame: Hour 0 (Baseline) ]
6. Dose administered of tazobactam at baseline [ Time Frame: Hour 0 (Baseline) ]
7. Change in plasma volume of distribution of amikacin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

   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

8. Change in plasma volume of distribution of piperacillin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

   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

9. Change in plasma volume of distribution of tazobactam during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

   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

10. Change in plasma clearance of amikacin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

    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

11. Change in plasma clearance of piperacillin during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

    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

12. Change in plasma clearance of tazobactam during the first 24 hours after administration [ Time Frame: First 24 hours of the antimicrobial treatment (Hour 1, Hour 5, Hour 7 and Hour 24) ]

    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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Arnaud FRIGGERI, MD; 478865647 ext +33; arnaud.friggeri@chu-lyon.fr

Contact: Alain LEPAPE, MD; 478861989 ext +33; alain.lepape@chu-lyon.fr

Locations

France

Service d'Anesthésie et Réanimation - Secteur de Soins Critiques, Groupement Hospitalier Sud, HCL; Recruiting

Pierre-Bénite, France, 69495

Contact: Arnaud FRIGGERI, MD 478865647 ext +33 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

Sponsors and Collaborators

Hospices Civils de Lyon

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT03990467
• Other Study ID Numbers: 69HCL17_0843
• First Posted: June 19, 2019
• Last Update Posted: September 30, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sepsis; Toxemia; Systemic Inflammatory Response Syndrome; Infections; Inflammation; Pathologic Processes; Shock; Tazobactam; Piperacillin; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action