Clinical trial NCT06766461: Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis
Official title: Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Sepsis - to Reduce Mortality in the Intensive Care Unit
Sepsis
Septic Shock
Keywords: sepsis
intensive care
critically ill
antibiotic
septic shock
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Maasstad Hospital
name: Albert Schweitzer Hospital
First posted: 2025-01-09
Enrollment: 980
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 28-day mortality
timeFrame: From enrollment to 28 days
Secondary outcomes:
measure: 90-day mortality
timeFrame: From enrollment to 90 days
measure: 365-day mortality
timeFrame: From enrollment to the 365 days
measure: ICU lengt of stay
timeFrame: From enrollment to the end of the study period at 12 months
measure: Hospital lengt of stay
timeFrame: From enrollment to the end of the study period at 12 months
measure: Time to shock reversal
timeFrame: From enrollment to the end of the study period at 12 months
measure: Microbiological eradication
timeFrame: From enrollment to hospital discharge
measure: Clinical cure
timeFrame: From enrollment to 14 days
measure: Plasma concentrations of the beta-lactam antibiotics
timeFrame: From enrollment to day 3
measure: Delta SOFA
timeFrame: From enrollment to day 3
measure: Delta Lactate
timeFrame: From enrollment to day 3
measure: Quality of life
timeFrame: 3 and 12 months after inclusion
measure: Medical consumption
timeFrame: 3 and 12 months after inclusion
measure: Productivity
timeFrame: 3 and 12 months after inclusion
measure: Adverse events and toxicity
timeFrame: From enrollment until the end of the study period at 12 months
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
Study officials:
References: