Paediatric Intensive Care Adaptive Platform Trial (PIVOTAL)
Critical illness
Current interventions as of 06/03/2026: PIVOTAL is a multi-centre, randomised, Bayesian adaptive platform trial which aims to evaluate multiple interventions simultaneously in paediatric intensive care. Patients who meet the platform eligibility criteria will 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 using the central web-based randomisation system Sealed Envelope. In circumstances where patients may later become eligible, pending a change to their condition or additional information becoming available, a second randomisation may be used for individual domains. Currently available domains: Fluid Domain: Patients receiving invasive mechanical ventilation in PICU will be eligible for the domain and must be randomised within 12 hours of meeting the platform and domain inclusion criteria. If the patient is deemed eligible, they will be randomised on a 1:1 basis to receive either of the following: 1. Conservative fluid management, this is comprised of two components: (i) conservative fluid administration and (ii) active fluid removal 2. Usual fluid management The intervention will continue until the end of study day 7 or the child is no longer on organ support or PICU discharge, whichever comes first. Sedation Domain: Patients receiving invasive mechanical ventilation and receiving or about to receive a continuous IV sedative will be eligible for the domain and must be randomised within 12 hours of meeting the platform and domain inclusion criteria. If the patient is deemed eligible, they will be randomised to receive one of the following: 1. Continuous IV infusion of dexmedetomidine 2. Continuous IV infusion of clonidine 3. Continuous IV infusion of midazolam As some sites may not enrol patients to one of the interventions, the randomisation ratios may be adjusted from equal randomisation for some intervention combinations to achieve 1:1:1 randomisati
Current key inclusion criteria as of 06/03/2026: 1. Gestational age at birth ≥37 weeks, or combined gestational age and post-birth age ≥37 weeks, and 2. Face-to-face contact with PICU or transport team staff 3. Receiving at least one of respiratory, cardiovascular or renal support 4. Expected to remain on organ support the following day 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. Fluid domain: 1. Receiving invasive mechanical ventilation Sedation domain: 1. Receiving invasive mechanical ventilation 2. Receiving, or about to receive, a continuous intravenous (IV) sedative Blood transfusion thresholds domain: Non-cardiac stratum: Hb ≤85 g/L in children without acute brain injury or Hb ≤100g/L in children with acute brain injury Cardiac stratum: Hb ≤100 g/L in children aged >28 days (non-neonate) or Hb ≤120g/L in children aged ≤28 days (neonate) _____ Previous key inclusion criteria: Platform inclusion criteria: 1. Gestational age at birth ≥37 weeks, or combined gestational age and post-birth age ≥37 weeks, and <16 years at the time of randomisation 2. Face-to-face contact with PICU or transport team staff 3. Receiving at least one of respiratory, cardiovascular or renal support 4. Expected to remain on organ support the following day 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 delayed reveal may be used for individual domains. Fluid domain: 1. Receiving invasive mechanical ventilation Sedation domain: 1. Receiving invasive mechanical ventilation 2. Receiving, or about to receiv
Current key exclusion criteria as of 06/03/2026: Platform exclusion criteria: 1. Death perceived as imminent 2. Previously recruited to a domain in PIVOTAL either in the last 30 days or during the same hospital admission Fluid domain: 1. Admitted with a condition that requires a specific fluid management regimen (e.g. diabetic ketoacidosis, tumour lysis syndrome, diabetes insipidus) 2. Participating in another research study that determines fluid management 3. Receiving renal replacement therapy (RRT) or Extracorporeal Membrane Oxygenation (ECMO) 4. Over 12 hours since meeting the platform and domain inclusion criteria Sedation domain: 1. Known hyper-sensitivity or contraindication to one of the sedative agents 2. Known pregnancy 3. Over 12 hours since meeting the platform and domain inclusion criteria Blood transfusion thresholds domain: 1. Haemoglobinopathies (e.g. sickle cell disease, thalassemia) where red blood cell transfusions may be used to prevent haemolytic or aggregation crises 2. Unrepaired cyanotic congenital heart disease and/or functionally single ventricle circulation and/or palliated parallel circulation 3. Known advance decision refusing blood/blood component transfusions (e.g. Jehovah’s Witnesses) 4. Receiving Extracorporeal Membrane Oxygenation (ECMO) 5. Receipt of RBC transfusion for a reason other than bleeding or extracorporeal support (on ECMO or for priming renal replacement circuit) since meeting the platform inclusion criteria _____ Previous key exclusion criteria: Platform exclusion criteria: 1. Death perceived as imminent 2. Previously recruited to a domain in PIVOTAL either in the last 30 days or during the same hospital admission 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 th