Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (The BATCH Trial)

DESIGN: Prospective, individually randomised, two-arm RCT with internal pilot study across 12-15 centres. PHASE 1: An internal pilot study to assess the recruitment rates, adherence to intervention, feasibility of individual randomisation, attrition rates, and the proportion of patients in whom we are able to measure both co-primary outcomes. Qualitative process evaluation which aims to improve the trial conduct in Phase 2. Defined stop-go criteria. PHASE 2: Two-arm RCT; PCT-guided best practice AMS management versus best practice AMS management alone. SETTING: Paediatric wards or PICUs. TARGET POPULATION: Hospitalised children <18 years being treated with IV antibiotics for suspected or confirmed bacterial infection. HEALTH TECHNOLOGIES BEING ASSESSED: The BATCH trial will assess the use of an additional PCT test in children hospitalised with suspected or confirmed bacterial infection, to guide antimicrobial prescribing decisions[1]. In children randomised to the intervention arm, a PCT test will be performed in the hospital laboratory at baseline and every 1-3 days whilst on on IV antibiotics. Children in the control arm will not have the PCT test performed. OUTCOMES AND SAMPLE SIZE: Co-primary outcomes: IV antibiotics duration (days) and a composite safety outcome comprising: unscheduled admissions/readmissions, re-instating IV antibiotic therapy and mortality. Secondary outcomes include total duration of antibiotics, time to discharge from hospital, health utility and other safety outcomes. A positive conclusion will be both a decrease in IV antibiotic duration AND non-inferiority in safety. Our observational study data showed an admission/re-admission rate of 8.8%. In critically ill patients, 3% re-instated IV antibiotic therapy, and 4% mortality was reported [2],[3]. With some overlaps considered, we estimate around 15% overall rate of our composite safety outcome. Assuming a conservative non-inferiority margin of 5%, a one-sided significance level of 0.05 and 90% power we would need 1748 participants. This will give 99% power to detect antibiotic duration decrease and 90% power to test non-inferiority in safety separately. STATISTICAL ANALYSIS: Our primary analysis of co-primary outcomes will a) compare the duration of days of IV antibiotics to assess the superiority of the intervention; b) compare the rate of the composite safety outcome to assess its non-inferiority in safety. Differences in total duration of antibiotics, time to discharge from hospital, health utility and other safety outcomes will also be compared as secondary outcomes. ECONOMIC EVALUATION: A cost-effectiveness analysis will be used to assess possible efficiency gains, and results presented in terms of costs per antibiotic treatment duration and per treatment of unmet primary safety endpoints. Using a NHS perspective, relevant direct medical costs and resource use (in-hospital and community) up to Day 28 will be collected. Health-related quality of life will be measured in children 5 years and older using CHU9D. Descriptive and regression analysis will be used to identify key elements of service use and cost and to explore the potential impact of baseline participant characteristics on the costs and outcomes measures. Differences in each arm will be used for the computation of an incremental cost-effectiveness ratio (ICER), and one way sensitivity analysis performed on key model parameters.