None listed
Conditions
Brief summary
Sepsis is a leading cause of death and disability in children globally accounting for over >3 million childhood deaths per year. Beta-lactam antibiotics are the most commonly used antibiotic to treat sepsis in children. Rather than giving a large dose of antibiotics intermittently, giving antibiotics over a longer time-period may improve outcomes, as seen in adult trials. To date, there is no high-grade evidence to support this practice in children. The BUILD trial is multicentre, multinational, open-label, type 1 adaptive hybrid effectiveness-implementation trial with an in-built pilot that will investigate if prolonged infusions of beta-lactam antibiotics increase survival for children with sepsis, while also checking safety and feasibility.
Interventions
Patients will be allocated 1:1:1 to one of the three treatment groups.
Arm 1 (Intervention 1), continuous infusion: Loading dose (calculated as per intermittent infusion) at randomisation. Continuous infusion to start at a time that is half the intermittent dosing interval. On first calendar day, the daily dose (less loading dose) is administered as a 24-hour infusion. Patients receive the daily dose as a 24-hour infusion on following calendar days.
Arm 2 (Intervention 2), extended infusion:
Patients will be allocated 1:1:1 to one of the three treatment groups. Arm 1 (Intervention 1), continuous infusion: Loading dose (calculated as per intermittent infusion) at randomisation. Continuous infusion to start at a time that is half the intermittent dosing interval. On first calendar day, the daily dose (less loading dose) is administered as a 24-hour infusion. Patients receive the daily dose as a 24-hour infusion on following calendar days. Arm 2 (Intervention 2), extended infusion: Antibiotic infused over 50% of the duration of the dosing interval (i.e., 3-hour infusion for 6-hourly dosing). Examples of antibiotics used - Meropenem, Cefotaxime, Piptazobactam. Dosing of the antibiotic will be determined by the clinician as per local institutional policy which is usually weight based. A registered nurse will administer the antibiotic. Antibiotic administration will be monitored for adherence by reviewing the PICU clinical information system or paper medical records.
Sponsors
The University of Queensland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
28 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
- Admitted to PICU - Aged >28 days to <18 years - Blood culture taken within the last 24 hours - One of the study beta-lactam antibiotics has been commenced within the previous 12 hours - Phoenix Sepsis Score greater than or equal to 2 points within 12 hours prior to, or the 12 hours post, commencement of beta-lactams (i.e. maximum recruitment window of 24 hours).
Exclusion criteria
- Premature neonates who are 12 hours - Cardiopulmonary arrest in the past two hours requiring cardiopulmonary resuscitation >2 min, or death is deemed to be imminent or inevitable - Already enrolled in a study deemed inappropriate for co-enrolment - Patients in whom end of life care has been instituted.
Outcome results
None listed