A Randomised Multiple Centre Trial of Conservative versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU)

Research Question: In critically-ill children referred as an emergency for paediatric intensive care and commenced on invasive mechanical ventilation and supplemental oxygen [Population], is a conservative oxygen saturation target of 88-92% [Intervention] superior to a liberal oxygen saturation target (95-100%) [Comparator] in terms of a composite of mortality and the number of days free of organ support in the next 30 days [Outcome]? DESIGN: Multiple centre open, parallel group RCT with integrated economic evaluation SETTING: 15 paediatric intensive care units (PICUs) and associated retrieval services TARGET POPULATION: Critically ill children referred as an emergency to a participating PICU commenced on invasive mechanical ventilation and supplemental oxygen. INCLUSION CRITERIA: (1) Age >38 weeks corrected gestational age and <16 years; (2) unplanned PICU referral; (3) commenced on invasive mechanical ventilation with supplemental oxygen; and (4) within 6 hours of face-to-face contact with PICU staff or retrieval team. EXCLUSION CRITERIA: Death perceived as imminent; brain pathology/injury as primary reason for admission; known pulmonary hypertension; known or suspected uncorrected congenital cardiac disease; known sickle cell disease, end-of-life care plan in place with limitation of resuscitation; receiving long-term mechanical ventilation prior to this admission; or recruited to Oxy-PICU in a previous admission. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve a peripheral oxygen saturation (SpO2) target of 88-92% during invasive mechanical ventilation. COMPARATOR: Adjustment of ventilation and inspired oxygen settings to achieve a SpO2 target of =95% during invasive mechanical ventilation. CONSENT: Research without prior consent model where written informed consent will be deferred to after randomisation due to the emergency nature of the treatment. PRIMARY OUTCOME: Composite outcome of death and days of organ support at 30 days (clinical effectiveness) and incremental costs, quality-adjusted life years (QALYs) and net monetary benefit at 12 months (cost effectiveness). OTHER OUTCOMES: - -Incremental costs at 30 days -Mortality at PICU discharge, 30 days, 90 days and 12 months -Time to liberation from ventilation -Duration of organ support -Length of PICU and hospital stay -Functional status at PICU discharge -Health-related quality of life (HrQoL) at 12 months SAMPLE SIZE: The primary outcome will be analysed using rank-based methods, with death at 30 days ranked as the worst outcome. To achieve 90% power, using simulations based on data from the Oxy-PICU pilot RCT, to detect a clinically meaningful reduction in the mean duration of organ support of 12 hours from 120 to 108 hours and assuming no impact on 7.5% mortality requires a total sample size of 2040 patients (allowing for withdrawal/refusal of deferred consent of 10%) A single interim analysis will be undertaken. TIMELINE: Total 48 months (HRA approval 1-4; site approvals/initiations 5-12; patient recruitment 7-30; internal pilot 7-12; follow-up 19-42; analysis/dissemination 33-48). ANTICIPATED IMPACT: It is anticipated that if a more permissive oxygen threshold is found to be clinically and cost-effective, implementation of these outputs into clinical guidelines and adoption into the NHS routine practice, will ensure a more efficient use of scarce NHS resources.