Discussion
infection
INFECTION, RECRUITMENT
The pilot cRCT was representative, in terms of sites and patients when compared with the whole UK PICU population and our analysis suggests a definitive trial is feasible. Several design modifications would need to be included in a definitive cRCT to ensure that the efficiency of trial processes is maximised.The cluster randomisation model was effective and supported by staff and parents. PICUs were able to be randomised into groups which were relatively evenly split in terms of unit size, and patient characteristics including age, ethnicity and admitting diagnosis.The contracted nature of the pilot cRCT meant that staff had to adapt practice more quickly than would be expected in a definitive cRCT, where a more prolonged and intensive support could be planned and instituted.The potential recruitment rate for a future definitive cRCT trial is similar to the pre-trial estimated rate value of 3 per site per week. One site from the intervention group closed to recruitment early due to reaching their recruitment target, which could have an impact in a definitive cRCT. Even though there are limited PICUs in the UK, the sample size simulations indicated that there are sufficient available clusters to adequately power a definitive cRCT on patient centred clinical outcomes, including health care acquired infection and days alive and free from ventilation.Each of the study periods (e.g. ecology, transition, intervention) need to be long enough to embed the new processes into clinical practice and the timeline. A definitive trial would need to ensure contracting of sites required enrolment of patients for the full period of the cRCT.Screening and recruitment processes worked efficiently, with the majority of eligible patients enrolled into the study across the ecology periods and Periods One and Two. Some eligible patients may have been missed due to the subjective estimate of whether the patient was likely to be extubated within the next 48 h.When comparing against the potentially eligible patients within the participating sites, patients enrolled were representative in terms of age and ethnicity. However, the need for translated material potentially limited inclusion of those parents who did not speak English.Sites implemented the consent model inconsistently, especially early in the pilot cRCT, with a number of parents not being approached for additional samples or data collection. Parents did not object to the consent process, as long as additional samples were only taken with consent. This was evident, as consent for routine data collection was good, but there was a number of refusals for collection of additional samples.Adherence to the SDD intervention was high, with SDD commencing in a timely manner in most children. The time-critical nature of the study intervention made delivery challenging and has resource implications. There appeared to be subtle differences in how staff described the nature of the intervention at sites administering SDD, which may have led to parental misconceptions.A definitive cRCT would need to ensure parental communication is clear about the design of the study and the experimental nature of SDD in an infection control regime. Information and training to engage those staff who were unsure or opposed to SDD will be vital to ensure equipoise in the intervention. The time-critical nature of the intervention will need to be considered in the funding model for a definitive cRCT to ensure site staff felt able to deliver workload.With regards to the ecological outcomes, the consent rate was low for the collection of additional samples. Staff reported challenges to these samples which were perceived as a burden on the patient and staff capacity, particularly during nights shifts, although when consent was obtained, sample collection was very high. An assessment of the ecology impact of SDD is crucial and a future definitive cRCT should consider including admission and discharge ecology monitoring as part of the SDD administration protocol, in order to minimise the burden of consent and ensure antimicrobial resistance is monitored as part of the trial intervention. Traditionally SDD trials have used rectal, rather than perineal swabs to monitor antimicrobial resistance but routine clinical screening uses the latter so we opted for this as a more practical and pragmatic intervention.