Are Standard Dosing Regimens of Piperacillin-Tazobactam Suitable in Critically Ill Patients With Open Abdomen and Negative Pressure Wound Therapy? A Population Pharmacokinetic Study.

Critical Illness Clinical Trial

— PK-LAP  

Official title:

Are Standard Dosing Regimens of Piperacillin-Tazobactam Suitable in Critically Ill Patients With Open Abdomen and Negative Pressure Wound Therapy? A Population Pharmacokinetic Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04915872
• Other study ID #: CHUBX 2020/53
• Status: Completed
• Start date: July 1, 2021
• Est. completion date: January 27, 2023

Study information

• Verified date: February 2023
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

For several years, open abdomen with temporary abdominal closure using Negative Pressure Therapy (OA/NPT) has become one of the leading strategies to treat or prevent intra-abdominal hypertension in critically ill surgical patients after a wide range of complex abdominal injuries and conditions. According to current practice, piperacillin-tazobactam (PTZ) is widely used as part of empirical combined antibiotic therapy to treat severe abdominal infections in the critically ill patients. On the other hand, little is known about the impact of OA/NPT on antibiotics pharmacokinetics and pharmacodynamics (PK/PD) and the optimal dosing regimens in this population remain unclear. As PTZ is a small hydrophilic molecule with a very low level of protein binding, invesitigators hypothesized that OA/NPT should lead to significant changes in volume of distribution (Vd) and/or drug clearance (CL The main objective of this study was to assess the incidence of underdosing and the pharmacokinetics of piperacillin in critically ill patients with OA/NPT. The secondary objective was to assess the appropriateness of recommended regimens for empirical minimum inhibitory concentration (MIC) coverage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: January 27, 2023
• Est. primary completion date: November 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18
• Admitted in surgical ICU for a suspected length of stay > 3 days
• Receiving an antimicrobial therapy by PTZ
• For an intra-abdominal infection
• Under OA/NPT during antimicrobial therapy
• With urinary and arterial catheters

Exclusion Criteria:

• Severe renal failure (CLCR < 30 ml/min) without indication for continuous renal replacement therapy (CRRT)
• Known allergy to PTZ
• Patient's refusal for participation to the research
• Patient unable to consent (dementia or severe psychiatric disorders, people under legal protection, people deprived of their liberty...)
• Pregnancy or breast-feeding

Related Conditions & MeSH terms

• Critical Illness
• Laparotomy

Intervention

Procedure:
• Blood sampling (T0, inclusion)
Blood sample (5 ml) at 30 minutes after the loading dose of 4g/0.5g over 30 minutes for therapeutic drug monitoring at peak concentration (Cmax)
• other samplings (T1)
- T1 : Day of the first surgical revision, under PTZ administered by continuous infusion : Blood sample (5 ml) for therapeutic drug monitoring at steady state concentration (Css). Urinary sample and collection of urinary volume between T0 and T1 (Urinary Clearance) NPT fluid sample and collection of NPT volume between T0 and T1 (Peritoneal Clearance) Peritoneal sampling for therapeutic drug monitoring at the site of infection (CPt)

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of piperacillin	The main outcome investigated in this study was the rate of piperacillin (PIP) underdosing, arbitrarily defined by at least one of three samples under 16 mg/L. This threshold represents the highest MIC for Pseudomonas as per the European Committee on Antimicrobial Susceptibility Testing (EUCAST).	T1 (Day of the first surgical revision, up to 72 hours after inclusion)