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

Erasmus University

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Double dosing of beta-lactam antibiotic

Study type: Interventional

Funder types: Other

Identifiers

NCT06766461

2024-512950-13-00 (EU Trial (CTIS) Number)

10140022310046 (Other Grant/Funding Number)

U1111-1308-9223 (Registry Identifier)

2024-512950-13

Details and patient eligibility

About

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.

Full 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.

Enrollment: 980 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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980 participants in 2 patient groups

Control

No Intervention group

Description:

This arm will receive standard of care according to local protocol.

Intervention

Experimental group

Description:

This arm will be treated with double dosages of beta-lactam antibiotics the first 48 hours after inclusion.

Treatment:

Drug: Double dosing of beta-lactam antibiotic