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

Sponsor

Centre Hospitalier Universitaire de Besancon (Other)

Overall Status

Unknown status

CT.gov ID

NCT02820987

Collaborator

(none)

129

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock	Drug: MEROPENEM Drug: PIPERACILLIN-TAZOBACTAM Drug: CEFEPIME	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

129 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Sep 1, 2016

Anticipated Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: MEROPENEM Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion.
Active Comparator: 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.	Drug: PIPERACILLIN-TAZOBACTAM Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion.
Active Comparator: 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.	Drug: CEFEPIME Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion.

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: MEROPENEM

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

Active Comparator: 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.

Drug: PIPERACILLIN-TAZOBACTAM

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

Active Comparator: 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.

Drug: CEFEPIME

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

Outcome Measures

Primary Outcome Measures

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

All cause mortality [28th day]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Pregnancy
Central nervous system infection
Burns

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chu Besancon	Besançon		France	25000

Sponsors and Collaborators

Centre Hospitalier Universitaire de Besancon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Centre Hospitalier Universitaire de Besancon

ClinicalTrials.gov Identifier:

NCT02820987

Other Study ID Numbers:

15/493

First Posted:

Jul 1, 2016

Last Update Posted:

Jul 17, 2018

Last Verified:

Jul 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Keywords provided by Centre Hospitalier Universitaire de Besancon

Septic shock, Beta Lactams, Extended infusion, PK/PD

Additional relevant MeSH terms:

Piperacillin, Tazobactam Drug Combination

Study Results

No Results Posted as of Jul 17, 2018