Critical illness Other
Conditions
Interventions
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 c
Sponsors
Great Ormond Street Hospital for Children NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
0 Years to 16 Years
Inclusion criteria
Inclusion criteria: 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 28 days (non-neonate) or Hb <120g/L in children aged =28 days (neonate)
Exclusion criteria
Exclusion criteria: 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 their condition/additional information available, a delayed reveal may be used for individual domains. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Clinical outcome: Ordinal outcome of death or days alive and free from organ support to day 30. Organ support will be defined as receipt of respiratory, cardiovascular, or renal support within PICU according to the Paediatric Critical Care Minimum Dataset. This will be measured from medical records and linkage to death registrations and PICANet. 2. Health economic outcome: Incremental net benefit at 180 days will be assessed using data from linkage to national hospital episode statistics, death registrations and PICANet. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Duration of PICU and hospital stay measured from medical records and linkage to PICANet at the relevant timepoints 2. 90- and 180-day mortality post-randomisation measured from medical records and linkage to death registrations and PICANet 3. Serious adverse events/reactions during the PICU stay (censored at 30 days post-randomisation) collected from medical records 4. Health-related quality of life at 180 days measured using age-appropriate PedsQL questionnaire | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactTasnin;Irene Shahid;Chang
;
Outcome results
None listed