Beta-lactam Infusion Group (BLING II)
Beta-lactam antibiotics are commonly used to treat life-threatening infections in critically ill patients. As a class of antibiotics, beta-lactams are known as time-dependent antibiotics because they have their greatest effect when the antibiotic concentration in the blood remains above a critical level (dependent on the organism) for the duration of the course.
Continuous infusion of beta-lactams has been shown to more consistently achieve these time-dependent pharmacodynamic endpoints than the standard practice of bolus dosing. However, the relatively small randomised controlled trials to date have not reported improved clinical outcomes, such as resolution of infection or lower mortality, with the use of continuous infusion. Current usage of continuous infusions for beta-lactam antibiotics is currently low in Australia and New Zealand.
To determine if continuous beta-lactam infusion results in increased Intensive Care Unit (ICU)-free days up to Day 28, compared with standard intermittent beta-lactam dosing in critically ill patients with severe sepsis.
The BLING II study is a multi-centre, double-blinded, double-dummy, randomised, controlled trial of continuous beta-lactam infusion versus intermittent beta-lactam bolus dosing for patients who are commenced on the following antibiotics, with administered dose determined by the treating clinician: ticarcillin-clavulanate, meropenem and piperacillin-tazobactam. For patients where the study drug is subsequently switched to flucloxacillin or dicloxacillin (e.g. for Staphylococcus aureus bacteraemia) or escalated to meropenem within 14 days of randomisation, the new beta-lactam will continue as the blinded study drug via the randomised administration method.
420 patients (210 in each group) will be enrolled in this study.
BLING II is a collaborative project, co-ordinated by Royal Brisbane and Women’s Hospital and the University of Queensland. The George Institute is in charge of the monitoring in this project.
The beta-lactam antibiotic chosen by the treating physician will be randomised to continuous infusion or intermittent bolus administration. The dose and dosing interval of the antibiotic will be chosen by the treating physician so as to reflect body size and estimated drug clearance. The dose of antibiotic will be the same regardless of treatment group allocation and antibiotic dosing can be modified during the study based on predicted or actual changes to renal clearance. Central randomisation will be performed with randomisation stratified within study sites. Sites will be provided with a series of opaque sealed envelopes labelled by Study Number and containing allocation status.
The study drug will be commenced as an open-label bolus of the antibiotic in both groups and antibiotic treatment will not be delayed by participation in the study.
For patients where the study drug is switched to flucloxacillin or dicloxacillin (e.g. for Staphylococcus aureus bacteraemia) or escalated to meropenem within 14 days of randomisation, the new beta-lactam will continue as the blinded study drug via the randomised administration method. Study drug administration will cease when the treating clinician determines that the duration of administration of the study drug has been sufficient up to 6a maximum of 14 days after randomisation or on discharge from the ICU, whichever occurs first.
Only one study drug will be administered in a blinded fashion at any one time.
Recruitment completed in April 2014. Monitoring and data cleaning phase has commenced with the database lock date set for the 18th August 2014.