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

Centre Hospitalier Universitaire de Besancon

Status and phase: Completed; Phase 3

Conditions: Septic Shock

Treatments: Drug: CEFEPIME; Drug: PIPERACILLIN-TAZOBACTAM; Drug: MEROPENEM

Study type: Interventional

Funder types: Other

Identifiers

NCT02820987

15/493

Details and patient eligibility

About

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

Full 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.

Enrollment: 119 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• Pregnancy
• Central nervous system infection
• Burns

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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119 participants in 3 patient groups

MEROPENEM

Active Comparator group

Description:

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.

Treatment:

Drug: MEROPENEM

PIPERACILLIN-TAZOBACTAM

Active Comparator group

Description:

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.

Treatment:

Drug: PIPERACILLIN-TAZOBACTAM

CEFEPIME

Active Comparator group

Description:

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.

Treatment:

Drug: CEFEPIME