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

Phase 4

Recruiting

• Conditions: Sepsis - to Reduce Mortality in the Intensive Care Unit; Sepsis; Septic Shock
• Interventions: Drug: Double dosing of beta-lactam antibiotic

• Registration Number: NCT06766461
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study First Submitted: 2024-11-27
• Status Verified: 2025-01
• Study Start: 2025-01-03
• Study First Submitted QC: 2025-01-08
• Last Update Submitted: 2025-01-08
• Study First Posted: 2025-01-09
• Last Update Posted: 2025-01-09
• Primary Completion: 2026-12-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 980

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Double dosing of beta-lactam antibiotic	This arm will be treated with double dosages of beta-lactam antibiotics the first 48 hours after inclusion.

Primary Outcome Measures

Name	Time	Method
28-day mortality	From enrollment to 28 days

Secondary Outcome Measures

Name	Time	Method
90-day mortality	From enrollment to 90 days
365-day mortality	From enrollment to the 365 days
ICU lengt of stay	From enrollment to the end of the study period at 12 months
Hospital lengt of stay	From enrollment to the end of the study period at 12 months
Time to shock reversal	From enrollment to the end of the study period at 12 months	From enrollment to the use of \<0.1 gamma of vasopressors for 4 consecutive hours.
Microbiological eradication	From enrollment to hospital discharge	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.
Clinical cure	From enrollment to 14 days	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)
Plasma concentrations of the beta-lactam antibiotics	From enrollment to day 3	Through concentrations take once a day for 3 consectutive days after enrollment. Target attianment is defined as 100%fT\>4xMIC
Delta SOFA	From enrollment to day 3	SOFA at day 3 - SOFA at admission
Delta Lactate	From enrollment to day 3	Lactate at day 3 - lactate upon inclusion
Quality of life	3 and 12 months after inclusion	EQ-5D-5L, a quetionnaire scoring 1 to 5 points on 5 domains. A higher score means a worse outcome.
Medical consumption	3 and 12 months after inclusion	iMTA Medical Consumption questionnaire
Productivity	3 and 12 months after inclusion	iMTA Productivity questionnaire
Adverse events and toxicity	From enrollment until the end of the study period at 12 months

Trial Locations

Locations (1)

Maasstad Ziekenhuis; 🇳🇱 Rotterdam, Netherlands