Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis

Phase 4RecruitingNCT06766461

Erasmus Medical Center980 enrolled

Overview

The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis.

Objective To determine if using higher dosages of beta-lactam antibiotics in the initial phase of sepsis improves clinical outcome of critically ill patients. Main trial endpoints The main trial endpoint is all cause 28-day mortality. Secondary trial endpoints Secondary trial endpoints include: Hospital length of stay, ICU length of stay, microbiological eradication, time to shock reversal, clinical cure, Δ Lactate, Δ PCT, Δ SOFA, 90- day mortality, 365-day mortality, pharmacodynamic target, post study calculation of the costs in both study, groups, EQ5D questionnaire 3 and 12 months after Admission, iMTA productivity questionnaire 3 and 12 months after admission, iMTA medical consumption questionnaire 3 and 12 months after admission and the number of adverse events. Trial design This is an open label, randomized controlled trial. Trial population The trial population will consist of adult patients admitted to the intensive care department with sepsis who will be treated according to protocol with beta-lactam antibiotics. Interventions During the trial participants in the intervention group will receive a double dose of antibiotics for the first 48 hours in comparison to the standard dose in the control group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

980

Conditions

Sepsis - to Reduce Mortality in the Intensive Care Unit Sepsis Septic Shock

Interventions

Double dosing of beta-lactam antibioticDRUG

This arm will receive double dosing of beta-lactam antibiotics for the first 48 hours after inclusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ≥18 years of age * Receiving intravenous antibiotic therapy of the target drugs (including continuous infusion of beta-lactam antibiotics) * Primary infection * Admitted to the ICU * Meeting the Sepsis-3 criteria for septic shock: sepsis in addition to shock requiring the start of vasopressors to maintain a mean arterial pressure 65 mmHg or greater, and a serum lac tate level greater than 2.0 mmol/L following "adequate fluid resuscitation". Exclusion Criteria: * Patient or legal representative not available to give informed consent within 72 hours after admittance * Pregnancy * Admittance for burn wounds * Patients receiving target antibiotics only as prophylaxis within the context of Selective Diges tive tract Decontamination (SDD) * Enrolment in another interventional trial * Patient received the study antibiotic for more than 24 hours before inclusion * Patient receiving extracorporeal membrane oxygenation (ECMO) * Patient is already treated with a double dose of antibiotics based on suspected infection

Locations (1)

Maasstad Ziekenhuis

Rotterdam, Netherlands

RECRUITING

Outcomes

Primary Outcomes

28-day mortality

Time frame: From enrollment to 28 days

Secondary Outcomes

90-day mortality

Time frame: From enrollment to 90 days

365-day mortality

Time frame: From enrollment to the 365 days

ICU lengt of stay

Time frame: From enrollment to the end of the study period at 12 months

Hospital lengt of stay

Time frame: From enrollment to the end of the study period at 12 months

Time to shock reversal

From enrollment to the use of \<0.1 gamma of vasopressors for 4 consecutive hours.

Time frame: From enrollment to the end of the study period at 12 months

Microbiological eradication

Eradication of the causative organism from the primary source up to 30 days after therapy when confirmed by at least one repeated culture. In cases where there were no repeat cultures and the patient had resolution of the infection, microbial eradication will be presumed.

Time frame: From enrollment to hospital discharge

Clinical cure

Completion of β-lactam antibiotic by day 14 without recommencement of antibiotics within 48hrs of cessation for same infective episode (investigator assessment of clinical response)

Time frame: From enrollment to 14 days

Plasma concentrations of the beta-lactam antibiotics

Central Contacts

Birgit C.P. Koch, PharmD

CONTACT

0031107033202 b.koch@erasmusmc.nl

Data from ClinicalTrials.gov

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