A platform trial to identify the best treatments for critically ill children admitted to paediatric intensive care
| ISRCTN | ISRCTN22370354 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22370354 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 1012497 |
| Protocol serial number | 23IF39 |
| Sponsor | Great Ormond Street Hospital for Children NHS Foundation Trust |
| Funder | Health Technology Assessment Programme |
- Submission date
- 13/09/2025
- Registration date
- 05/12/2025
- Last edited
- 05/12/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English summary of protocol
Background and study aims
There is an urgent need to improve treatment for critically ill children on paediatric intensive care units (PICUs). Randomised controlled trials provide the best evidence, but the way we do these trials is slow and expensive. It usually takes several years for enough children to be included in a study before we have enough information to tell which treatment is safer. A randomised adaptive platform is an alternative way of doing trials. It allows multiple treatments and research questions to be tested at the same time under one platform. An important feature is that the trial can 'adapt' as it goes along. For example, new treatments or research questions can be added when they become available. The results are also looked at during the trial, not just at the end. This means treatments that are working better in the trial can be given to more patients sooner, while those that are less safe or less effective can be stopped earlier. The primary objective is to evaluate multiple widely used treatments at the same time to improve clinical care for critically ill children on PICU, initially focusing on evaluating three treatment areas.
Who can participate?
Patients aged under 16 years who have face-to-face contact with PICU or transport team staff, are receiving at least one of respiratory, cardiovascular, or renal support, and are expected to remain on organ support the following day.
What does the study involve?
Patients who meet the platform-level eligibility will be assessed against specific treatment area eligibility criteria. Those eligible for one or more treatment areas will be enrolled into the trial. Patients will be followed up to 6 months after enrolment.
What are the possible benefits and risks of participating?
All treatments and strategies used in the PIVOTAL study are commonly used in PICU and reflect current practice in the UK so there is a little additional risk to participants. There is no guarantee that participating in this study will directly benefit the participants but may help to improve future care and outcomes for children in PICU requiring organ support. All participants, regardless of which domain or treatment group they are in, will be monitored closely for any side-effects or serious adverse events by the site teams.
Where is the study run from?
The study is coordinated by the Intensive Care National Audit & Research Centre (ICNARC) (UK)
When is the study starting and how long is it expected to run for?
January 2026 to March 2030
Who is funding the study?
National Institute for Health and Care Research (NIHR) – Health Technology Assessment Programme (UK)
Who is the main contact?
Tasnin Shahid, PIVOTAL@icnarc.org
Contact information
Scientific, Principal investigator
30 Guildford Street
London
WC1N 1EH
United Kingdom
| Phone | +44 (0)20 78138118 |
|---|---|
| mark.peters@ucl.ac.uk |
Public
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
| Phone | +44 (0)20 45136238 |
|---|---|
| PIVOTAL@icnarc.org |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open randomized controlled parallel-group Bayesian adaptive platform trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Paediatric Intensive Care Adaptive Platform Trial (PIVOTAL) |
| Study acronym | PIVOTAL |
| Study objectives | The principal research question aims to find out the effect of a range of intervention(s) to improve outcomes for critically ill children receiving organ support (for example to help their breathing, heart or kidneys) on a paediatric intensive care unit. This is defined by the outcome death or days alive and free from organ support to day 30 (this encompasses both survival and the number and duration of organs supported). The primary health economic objective is to investigate the effect of the intervention(s) on incremental net-benefit at 180 days. The secondary objectives are to investigate the effect of the intervention(s) on other important patient-, family- and healthcare-centred outcomes. |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Critical illness |
| Intervention | 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 delayed reveal 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 Patients will initially be randomised 1:1:2 to dexmedetomidine, clonidine and midazolam in the non-cardiac stratum and 1:1:3 in the cardiac stratum for those sites offering all interventions. Patients will be randomised 1:1 to dexmedetomidine and clonidine in those sites opting out of midazolam. The intervention will continue until clinical decision to discontinue or 30 days after randomisation, whichever comes first. Blood Transfusion Thresholds Domain: Patients with a Hb less than or equal to the relevant threshold outlined below will be eligible for the domain: 1. Non-cardiac stratum: Hb <85g/L in children without acute brain injury or Hb <100g/L in children with acute brain injury 2. Cardiac stratum: Hb <100g/L in children aged >28 days (non-neonate) or Hb <120g/L in children aged ≤28 days (neonate) Where a patient meets all eligibility criteria at the time of randomisation, their allocation will be revealed immediately. In circumstances where patients may later become eligible, pending a change to their condition or additional information becoming available, a delayed reveal will be used. If the patient is deemed eligible, they will be randomised on a 1:1 basis to receive either of the following: 1. Restrictive transfusion strategy 2. Liberal transfusion strategy The intervention will continue until day 30 or PICU discharge, whichever comes first. |
| Intervention type | Drug |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Dexmedetomidine, clonidine, midazolam |
| Primary outcome measure(s) |
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. |
| Key secondary outcome measure(s) |
1. Duration of PICU and hospital stay measured from medical records and linkage to PICANet at the relevant timepoints |
| Completion date | 31/03/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 0 Years |
| Upper age limit | 16 Years |
| Sex | All |
| Target sample size at registration | 12900 |
| 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 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) |
| 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 |
| Date of first enrolment | 01/01/2026 |
| Date of final enrolment | 01/09/2029 |
Locations
Countries of recruitment
- United Kingdom
- England
- Northern Ireland
- Scotland
- Wales
Study participating centres
Cambridge
CB2 0QQ
England
Liverpool
L14 5AB
England
Birmingham
B4 6NH
England
Bristol
BS2 8BJ
England
Westminster Bridge Road
London
SE1 7EH
England
High Heaton
Newcastle upon Tyne
NE7 7DN
England
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
England
London
WC1N 3JH
England
Headington
Oxford
OX3 9DU
England
Leeds
LS1 3EX
England
Leicester
LE1 5WW
England
Derby Road
Lenton
Nottingham
NG7 2UH
England
London
SW3 6NP
England
London
E1 1FR
England
Manchester
M13 9WL
England
Stoke-on-trent
ST4 6QG
England
Sheffield
S10 2TH
England
Southampton
SO16 6YD
England
Tooting
London
SW17 0QT
England
London
W2 1NY
England
Edinburgh
Lothian
EH16 4TJ
Scotland
Glasgow
G51 4TF
Scotland
Heath Park
Cardiff
CF14 4XW
Wales
Belfast
BT12 6BA
Northern Ireland
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
05/12/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 05/12/2025.
15/09/2025: Study's existence confirmed by the HRA.
