Platform Trial in critically Ill children - PIVOTAL

There is an urgent need to learn more about how best to treat critically ill children on intensive care units. Randomised controlled trials (RCTs) provide the best evidence for the best treatments but the way we do these trials now is slow and expensive. Currently, only some very ill children are allocated to receive one of two alternative treatments in a single RCT. It usually takes several years for enough children to be included in a study before we think we have enough information to tell which treatment is safer. We must estimate how many children we will need to answer the question before we start. This whole process is inefficient. It can take 10 years to answer a single important research question. A randomised adaptive platform is an alternative way of doing trials. The idea is to allow multiple research questions and treatments to be tested at the same time. Another important feature is that the trial can 'adapt' or change design as it goes along. These changes may include adding in new treatments or important research questions when they become available. Other changes are that the results are looked at as the trial is going on not just at the end. This means that the treatments that are working better in the trial can be given to more patients. Also, less safe or less effective treatments are stopped sooner. We know from platform trials in the Covid-19 pandemic that this way of doing studies can answer more questions, more efficiently in less time. This has been highlighted as a priority for research on paediatric intensive care units (PICUs). We have done some work to help prepare for a platform trial in PICU. We have consulted with parents, young people and PICU doctors and nurses. They have helped us to agree what the most important research questions are and what things they most want us to measure as outcomes. We have also codeveloped rules we will use in the trial to make 'adaptations' including how certain we need to be to say treatment does or does not work and if it is cost-effective for the NHS. We now want to establish a PICU platform trial that aims to answer multiple important research questions at the same time to identify the best treatments for children admitted to PICU as quickly and efficiently as possible. To start with, we aim is to answer the following questions: 1. What is the best sedative agent for use in critically ill children requiring invasive mechanical ventilation? 2. Does a plan designed to avoid having too much fluid in the body improve outcomes for critically ill children? 3. Does using blood transfusions less often improve outcomes for critically ill children? These questions are based on topics prioritised by parents, young people and PICU doctors and nurses for research as part of research prioritisation exercises conducted by the Paediatric Critical Care Society and during our preliminary design work conduced as part of development of a PICU platform trial. Parents and young people will continue to provide an oversight role for PIVOTAL, through parent and young people advisory groups, and will provide perspectives on governance, research delivery for the initial questions and the prioritisation of future questions/interventions. Our longer-term aim is to provide an ongoing national platform to that will allow new treatments or questions to be added over time and to support early career researchers to gain experience.

This NIHR HTA funded Platform trial will test three common interventions (domains) Conservative fluid management, sedation drugs and Blood transfusion thresholds in critically ill children 0-17 years of age across UK PICUs