Title: A pilot cluster randomised clinical trial of the use of selective gut decontamination in critically ill children (Paediatric Intensive Care and Infection Control: PICnIC)
Funder: Department of Health and Social Care

Abstract: Background: Healthcare Associated Infections (HAI) are associated with adverse outcomes among critically ill children. Selective decontamination of the digestive tract (SDD) may reduce the risk of HAI by decolonising the oropharynx and gastrointestinal tract; however, evidence for its use in paediatric intensive care units (PICUs) is limited. Design: External pilot, parallel group, cluster-randomised clinical trial (cRCT) with integrated mixed-methods study. The pilot cRCT is intended as a miniature version of the potential definitive cRCT to test feasibility and study procedures. The mixed-methods study will use interviews, focus groups and surveys to explore the acceptability of the SDD intervention and proposed trial and procedures to health care professionals and parents/guardians Setting: Six PICUs. Trial population: Critically ill children, expected by the PICU clinician to be mechanically ventilated for at least 48 hours. Inclusion criteria: Age >37 weeks (corrected gestational age) and =18 years; receiving mechanical ventilation expected to last at least 48 hours. Exclusion criteria: Known allergy, sensitivity or interaction to polymixin E, tobramycin, or nystatin; known pregnant; death perceived as imminent. Health technology being assessed: SDD compared with usual care (standard infection control as per individual PICU protocol). SDD will comprise standard infection control measures combined with decolonisation of the oropharynx and gastrointestinal tract using a combination of 2% polymixin E, 2% tobramycin, 2% nystatin (oropharyngeal paste and nasogastric solution) for duration of mechanical ventilation (maximum 30 days). Outcomes: Acceptability of the intervention to health care professionals and to parents/guardians (assessed by exploring willingness to recruit and acceptability of consent process); adherence to the SDD intervention (assessed by proportion of eligible children allocated to the intervention that receive SDD); estimation of recruitment rate; and characteristics of potential outcome measures for the definitive cRCT. Sample size: The pilot cRCT will recruit from six PICUs over 18 weeks (8 weeks pre-intervention, 2 weeks transition and 8 weeks following introduction of the intervention in 3 randomly selected PICUs). The anticipated sample size is 324 children, of which 90 would receive SDD. Assuming an ICC of 0.05, this sample size would enable rate parameters (recruitment, adherence, follow-up) with an observed value of 80% or greater to be estimated with a precision of ±10% or less. The mixed-methods study will involve: focus groups (n=2) and interviews (n=~10) with participating PICUs; online survey in all PICUs; and surveys (n=~100) and interviews (until data saturation is reached, n=~15-25) Difference between current and planned care pathways: Current infection control focuses on preventing exposure to exogenous pathogens. In the planned care pathway, decolonisation of the oropharynx and gastrointestinal tract will reduce exposure to endogenous microorganisms. Timetable (months): Set-up (1-6); recruitment (7-11); culture collection/analysis (7-14); survey/interviews (7-13); follow-up/data validation (8-13); focus groups/survey (9-11); analysis/dissemination (14-18). Anticipated recruitment rate 3/PICU/week (PICANet data indicate ~4.5 children/PICU/week mechanically ventilated for =48 hours). Team expertise: PPI, PICU staff, pharmacy, microbiology, cRCTs, statistics

Lay abstract: Each year, around 20,000 children are admitted to paediatric intensive care units (PICUs) in the UK. Critically ill children are at a higher risk of hospital-acquired infections. Many of these infections are caused by bacteria in the digestive tract, such as those in the mouth and stomach. Normally there are high numbers of ‘good’ bacteria in the digestive tract. When someone is very poorly, the number of ‘good’ bacteria may be reduced by antibiotics, lack of feeds (if they cannot tolerate milk) and damage to the lining of the gut. As a result, some ‘bad’ bacteria may thrive in the digestive tract, and spread to other organs such as the lung (causing pneumonia) or the bloodstream (causing sepsis). All PICUs have several methods to reduce the risk of hospital-acquired infections, such as providing antibacterial gel on units. One possible method is to treat patients with antibiotics that stop the growth of bacteria in the digestive tract. This treatment is called selective decontamination of the digestive tract (SDD). It has been shown in adults to reduce the number of hospital-acquired infections and improve survival. However, it is unclear if it works in children. We also need to be sure that it does not lead to a rise in resistance to antibiotics either in the patient or in the whole community. Our aim is to compare giving SDD with not giving SDD (usual care) in children admitted to PICU. As large clinical trials are expensive, it is important to be confident a trial can be done and that the different components of the trial can all work together. Before embarking on a full trial, we will conduct an 18-month feasibility study including a pilot trial. A feasibility study is a piece of research done before the main trial to answer the question “Can this trial be done?” and is used to estimate important factors such as willingness of patients to take part. A pilot trial is a miniature version of the full trial and is done to check that the different components, such as recruiting patients, delivering treatment and follow-up, all run smoothly. Six PICUs will be randomly assigned to either deliver, or not, SDD to eligible patients. All PICUs will start off not delivering SDD. Then halfway through, three of them will switch to delivering SDD. This type of study is known as a cluster randomised controlled trial. It ensures that the two groups of units, and the patients in those units, are as similar as possible, except for the delivery and receipt of SDD. It therefore allows us to see whether SDD is any more or less beneficial than usual care. We will also take swabs to monitor levels of antibiotic resistant bacteria in all participating PICUs. A child can participate in the study if they are admitted to one of the six PICUs and are expected to be on a breathing machine for at least 48 hours. We plan to include up to 324 patients and estimate 90 will receive SDD. This study will also involve conducting interviews with parents of participating children to understand whether the study was acceptable to them, review how they were approached and the information provided, and what outcome measures are most important to them. We have patient and parent representatives as co-investigators on this study. They are involved in developing how the study will be done, and in overseeing the conduct and management of this study. Once the study is complete, we will report a clear recommendation, or not, for continuation to a full trial

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION