Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (BATCH): protocol for a randomised controlled trial

Abstract

IntroductionProcalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children.Methods and analysisBiomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic.Ethics and disseminationThe trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings.Trial registration numberISRCTN11369832.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study

“…Children in the control arm will not have the PCT test performed. The trial protocol [ 3 ] includes further detail on the implementation of the intervention.…”

“…Steps 2 and 3 are only relevant when step 1 has been adhered to, i.e., when a PCT result is available. In cases where the PCT result was available and was considered, this will be considered adherence to the intervention policy specified in the trial protocol, regardless of the actual clinical decision [ 3 ].…”

“…A screening log will be kept at each site. Screening procedures are described in the trial protocol [ 3 ].…”

“…BATCH (biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection) is a randomised controlled trial to compare PCT-guided management of severe bacterial infection in children with current management [ 3 ]. The primary research question is whether addition of PCT testing to current best practice based on the NICE antimicrobial stewardship guidelines [ 4 ] can safely allow a reduction in duration of antibiotic therapy in hospitalised children with suspected or confirmed bacterial infection compared to current best practice alone.…”

An Evaluation into Procalcitonin Levels in Full-Term Neonates Managed for Suspected Early Onset Sepsis due to Probable Maternal Intrapartum Sepsis

“…Among the different molecules investigated as biomarkers of sepsis, procalcitonin (PCT) seems to be the most utilized and is now established in the adult population and showed to be promising in paediatrics. 10, 11, 12 PCT is known to be of better diagnostic and prognostic value for bacterial infections. 13, 14 PCT produced by C cells of the thyroid gland is involved in maintaining serum calcium levels and released into the circulation in response to pro-inflammatory stimuli and endotoxins, specifically originating from bacteria.…”