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

NCT ID: NCT02820987

Last Updated: 2025-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

119 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-27

Study Completion Date

2018-10-04

Brief Summary

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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

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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.

Conditions

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Septic Shock

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

MEROPENEM

Intervention Type DRUG

Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion.

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.

Group Type ACTIVE_COMPARATOR

PIPERACILLIN-TAZOBACTAM

Intervention Type DRUG

Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion.

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.

Group Type ACTIVE_COMPARATOR

CEFEPIME

Intervention Type DRUG

Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion.

Interventions

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MEROPENEM

Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion.

Intervention Type DRUG

PIPERACILLIN-TAZOBACTAM

Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion.

Intervention Type DRUG

CEFEPIME

Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Pregnancy
* Central nervous system infection
* Burns
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chu Besancon

Besançon, , France

Site Status

Countries

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France

References

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Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. doi: 10.1186/cc9091. Epub 2010 Jul 1.

Reference Type RESULT
PMID: 20594297 (View on PubMed)

Winiszewski H, Despres C, Puyraveau M, Lagoutte-Renosi J, Montange D, Besch G, Floury SP, Chaignat C, Labro G, Vettoretti L, Clairet AL, Capellier G, Vivet B, Piton G. beta-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study. J Crit Care. 2022 Feb;67:141-146. doi: 10.1016/j.jcrc.2021.10.023. Epub 2021 Nov 9.

Reference Type DERIVED
PMID: 34768176 (View on PubMed)

Other Identifiers

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15/493

Identifier Type: -

Identifier Source: org_study_id

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