PIVOTAL: Paediatric Intensive Care Adaptive Platform Trial (PIVOTAL)

Research summary

PIVOTAL is a multi-centre, randomised, Bayesian adaptive platform trial in paediatric intensive care which aims to evaluate multiple important research questions at the same time, with an integrated economic evaluation, internal pilot phase, and patient follow-up at 6 months. The primary platform clinical objective is to investigate the effects of a range of intervention(s) on the ordinal outcome of death or days alive and free from organ support to day 30. The primary platform health economic objective is to investigate the effect of the intervention(s) on incremental net-benefit at 180 days. The secondary platform objectives are to investigate the effect of the intervention(s) on other important patient-,family and healthcare-centred outcomes. A domain refers to a defined therapeutic area or grouping of related interventions that are being investigated. Patients may be enrolled into more than one domain. Where this is the case, patients will receive only one intervention from each domain. To begin with, there will be three domains on the platform aiming to answer the following questions: 1. Does a plan designed to avoid having too much fluid in the body improve outcomes for critically ill children? 2. What is the best sedative agent for use in critically ill children requiring invasive mechanical ventilation? 3. Does using blood transfusions less often improve outcomes for critically ill children? Platform outcomes will be consistent across all domains. Individual domains may have additional, domain-specific secondary outcomes. Bayesian adaptive platform trials do not have a fixed participant recruitment number at the start. Instead, accumulating data will guide decisions during the trial. This means the trial can adjust as it goes i.e. stopping a domain early if results are clear or continuing if more information is needed. The first adaptive analysis is planned after 7 months of recruitment, after which adaptive analyses will be conducted every 4 months. We anticipate ~320 platform eligible patients per month across 20 paediatric intensive care units (PICUs). The maximum assumed sample size over the recruitment period is 12,900. Patients who meet the platform eligibility criteria will then be screened for each domain against the domain-specific eligibility criteria. Patients will be randomised if they are deemed eligible for one or more domains. In circumstances where patients may later become eligible, pending a change to their condition/additional information available, a second randomisation may be used for individual domains. Based on the domain eligibility a patient meets, they will be randomised to one of the study arms in the domain: DOMAIN: FLUID 1) Intervention: Conservative fluid management 2) Comparator: Usual fluid management DOMAIN: SEDATION 1) Intervention(s): - Continuous IV infusion of dexmedetomidine - Continuous IV infusion of clonidine 2) Comparator: Continuous IV infusion of midazolam DOMAIN: BLOOD TRANSFUSION THRESHOLDS 1) Intervention: Restrictive transfusion strategy 2) Comparator: Liberal transfusion strategy All other clinical care for patients will be determined by the clinical team responsible for the patient's care. Data will be collected daily whilst in PICU, alongside routine data collection. Patients will be followed up after 6 months to ascertain their quality of life. The study will use a deferred consent model due to the emergency nature of the patient population. Eligible patients will be randomised by the PICU and their parents/legal guardians will be approached for consent to continue in the study at the earliest appropriate opportunity.

Principal Investigator

Dr Avishay Sarfatti

Contact us

Email: childrensresearch@ouh.nhs.uk

IRAS number

1012497