Speakers
Padmanabhan Ramnarayan, MBBS, MD, FRCPCH, FFICM
Reader in Pediatric Critical Care
Imperial College London
Keywords
Pragmatic Clinical Trials
Key Points
- Sick children, when they are acutely ill, start with standard oxygen therapy, which escalates to noninvasive respiratory support (CPAP/BIPAP or high flow nasal cannula) before invasive ventilation support in the ICU. The difficulty with pediatric respiratory support is that the step-up and step-down of respiratory care is very evidence poor even though these therapies are used commonly.
- In 2016, we published a pilot trial looking at high-flow nasal cannula (HFNC) therapy compared to CPAP in pediatric critical care. What we found from the pilot RCT, was that there were two distinct populations, step-up (i.e., acutely ill patients) and step-down, which is the extubation or post-extubation part of the care pathway.
- The trial team established that it was feasible to randomize around 50% of patients and assessed the acceptability of deferred consent or retrospective consent, which was justified because the therapy often happens under emergency situations during a time of high stress for parents. The team was also able to generate some pilot data on outcomes such as reintubation rate and length of respiratory support to try and understand how we could take this forward in a trial.
- The trial team decided to create a master protocol, FIRST-line support for Assistance in Breathing in Children (FIRST-ABC), to compare HFNC with CPAP and package up both the acute illness (Step-up pragmatic RCT) and the post-extubation (Step-down pragmatic RCT) patients into this protocol to have two independently powered trials that shared the infrastructure and the cost effectiveness analysis.
- The FIRST-ABC trial adopted a pragmatic design with a heterogenous patient cohort where the indication to start NRS was based on physiological criteria, which allowed the results to be applicable to all situations where HFNC is started. There were pragmatic inclusion criteria of being admitted to PICU/HDU, age 36 weeks and older and less than 16 years, and assessed by the treating clinician to require noninvasive respiratory support either for an acute illness or within 72 hours of extubation following a period of invasive ventilation.
- The primary outcome for was the time to liberation from respiratory support defined as the start of a 48-hour period during which the child was free of all forms of respiratory support (excluding supplement oxygen). The step-up trial started recruitment in August 2019, 1,449 children were eligible, 600 children were randomized, and 595 consented. The primary analysis showed that HFNC was noninferior to CPAP in acutely ill children in critical care. The median time to liberation was 53 hours for the HFNC group and 48 hours for the CPAP group.
- For the step-down RCT, patient recruitment started in August 2019 with 587 patients consenting and 552 included in the primary analysis. The median time to liberation in the HFNC group was 50 hours and the CPAP group was 43 hours. HFNC was not noninferior to CPAP following extubation.
Learn more
Read more about the study in JAMA.
Discussion Themes
– Did you find there are clusters of clinicians that consistently found that they were unwilling to randomize someone? We had monthly teleconferences – some clinicians were not fussed about it. We did not see specific site patterns, but we did see some cohort patterns.
– What challenges did you face due to COVID-19? Many other trials in the country were behind and everyone else had to stop. We were fortunate that when the lockdowns were lifted everyone came back into action to complete recruitment during the time scheduled.
Tags
#pctGR, @Collaboratory1