PK/PD of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock

Phase 3

Completed

• Conditions: Septic Shock
• Interventions: Drug: MEROPENEM; Drug: PIPERACILLIN-TAZOBACTAM; Drug: CEFEPIME

• Registration Number: NCT02820987
• Lead Sponsor: Centre Hospitalier Universitaire de Besancon

Brief Summary

This study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock.

Detailed Description

Beta Lactams are the keystones of shock septic treatment. Early phase of septic shock is a period of disturbed pharmacokinetics, with augmented renal clearance and distribution volume of hydrophilic drugs as Beta Lactams. Consequently, early phase of septic shock is a period at risk of underdosing Beta Lactam, which could increase the risk of clinical failure an mortality.

Data are available concerning underdosing of MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME, when administered in bolus.

No data exist concerning the achievement of a target of 100% of the whole interval above 4 time the superior breakpoint of Pseudomonas Aeruginosa according to EUCAST (European Committee on Antimicrobial Susceptibility Testing), during the 48 first hours of treatment of septic shock, when Beta Lactam are administered in extended infusion.

Study Timeline

• Study First Submitted: 2016-06-29
• Study First Submitted QC: 2016-06-29
• Study First Posted: 2016-07-01
• Study Start: 2016-09-01
• Primary Completion: 2016-09-01
• Status Verified: 2018-07
• Study Completion: 2018-10-04
• Last Update Submitted: 2024-12-27
• Last Update Posted: 2024-12-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 119

Inclusion Criteria

• Septic shock
• Meropenem, piperacillin-tazobactam or cefepime started after enrollment

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Exclusion Criteria

• Pregnancy
• Central nervous system infection
• Burns

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEROPENEM	MEROPENEM	After enrollment, patients of MEROPENEM arm will receive an initial 2g bolus of MEROPENEM and 2g infusion over 3 hours every eight hours, during 48 hours, without modification of rhythm and dose according to renal function.
PIPERACILLIN-TAZOBACTAM	PIPERACILLIN-TAZOBACTAM	After enrollment, patients of PIPERACILLIN - TAZOBACTAM arm will receive an initial 4g bolus of PIPERACILLIN - TAZOBACTAM and a 16g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function.
CEFEPIME	CEFEPIME	After enrollment, patients of CEFEPIME arm will receive an initial 2g bolus of CEFEPIME and a 6g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function.

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving the PK/PD target	First 48 hours	Proportion of patients achieving the target of 100% of 48 first hours of treatment above 4 time the upper critical breakpoint for Pseudomonas Aeruginosa

Secondary Outcome Measures

Name	Time	Method
All cause mortality	28th day

Trial Locations

Locations (1)

Chu Besancon; 🇫🇷 Besançon, France