A study to define the platelet count below which critically ill patients should receive a platelet transfusion before an invasive procedure

ISRCTN	ISRCTN79371664
DOI	https://doi.org/10.1186/ISRCTN79371664
IRAS number	312405
Secondary identifying numbers	CPMS 53274, IRAS 312405

Submission date: 01/09/2022
Registration date: 30/09/2022
Last edited: 07/06/2024

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
Platelets are cells in the blood that help form clots and stop bleeding. People treated in a critical care unit often have a low number of platelets (platelet count) in their blood because they are very unwell. Platelet transfusions are made up of platelets collected from screened, healthy donors. Platelet transfusions are sometimes given before these procedures if the patient’s platelet count is low. This is thought to reduce the possible risk of bleeding from the procedure.
However, platelet transfusions also carry risks such as inflammation, infection, and allergic reactions, and may not work as effectively in unwell patients.
Currently, we do not know the platelet count below which giving a platelet transfusion might be beneficial. Surveys of doctors working in UK critical care units have shown uncertainty over the platelet count below which doctors should give a platelet transfusion. As a result, platelet transfusions are currently given to patients with a wide range of different platelet counts and there is no set threshold.
This study will test five different thresholds to find out the safest count below which platelet transfusions should be given before invasive procedures are carried out in intensive care.

Who can participate?
Patients aged 18 years and over who have accepted for admission or admitted to critical care, with a platelet count of less than 50 x 10e9/L who are being considered for a platelet transfusion for a low bleeding risk invasive procedure

What does the study involve?
Patients will be allocated to one of five platelet count thresholds (less than 10, 20, 30, 40 or 50). If their platelet count is below their allocated threshold, then they will receive a platelet transfusion before a low bleeding risk invasive procedure. Patients will remain in their allocated ‘group’ (threshold) for the duration of their critical care unit stay.
Some information about the patients’ hospital stay is collected from hospital medical records. Other important health information is collected from national health databases. Some patients will also be sent a short health questionnaire around 90 days and 1 year after becoming involved in the study. At the end of the study, all this information will allow us to compare the different transfusion thresholds in the study to find out which is most beneficial.

What are the possible benefits and risks of participating?
The benefit of receiving a platelet transfusion is to possibly reduce the risk of bleeding during an invasive procedure. The possible risks of receiving a platelet transfusion include inflammation, infection and allergic reactions. The purpose of this study is to look at the best platelet count threshold at which the possible benefits of platelet transfusion outweigh the possible risks, as this is currently unclear.

Where is the study run from?
University of Oxford (UK)

When is the study starting and how long is it expected to run for?
January 2022 to December 2026

Who is funding the study?
National Institute for Health Research (NIHR) – Health Technology Assessment Programme (UK)

Who is the main contact?
Hayley Noble, T4P@icnarc.org

Study website

Contact information

Ms Hayley Noble
Scientific

Intensive Care National Audit & Research Centre (ICNARC)
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom

Phone	+44 (0)20 7269 9277
Email	T4P@icnarc.org

Prof Peter Watkinson
Scientific

Nuffield Department of Clinical Neurosciences
Kadoorie Centre for Critical Care Research and Education
The Chancellor Masters and Scholars of the University of Oxford
Oxford
OX3 9DU
United Kingdom

ORCID ID	0000-0003-1023-3927
Phone	+44 (0)1865 220 621
Email	Peter.watkinson@ndcn.ox.ac.uk

Study information

Study design	Randomized; Interventional; Design type: Treatment, Other
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	The Threshold for Platelets (T4P) study: a prospective randomised trial to define the platelet count below which critically ill patients should receive a platelet transfusion prior to an invasive procedure
Study acronym	T4P
Study hypothesis	That platelet transfusion in critically ill patients has net clinical and monetary benefit only below certain thresholds where any gain of preventing bleeding exceeds harm from exacerbating inflammatory and/or infective processes.
Ethics approval(s)	Approved 08/07/2022, South Central – Oxford C Research Ethics Committee (Health Research Authority (Bristol), Ground Floor, Temple Quay House, 2 The Square, BS1 6PN, UK; +44 (0)207 104 8226; oxfordc.rec@hra.nhs.uk), ref: 22/SC/0186
Condition	Critical care
Intervention	Current interventions as of 07/06/2024: T4P is a large-scale, multi-centre, data-enabled, registry-embedded, open-label, randomised, comparative effectiveness trial with an internal pilot across five equally spaced platelet count thresholds (<10 - <50 x 10e9/L). There will be an integrated economic evaluation. The trial plans to include 2550 critically ill patients recruited from 66 NHS adult critical care units over a period of 42 months. The normal platelet count is 150-450 x 10e9/L. Patients whose platelet count is below 50 x 10e9/L (at any time in their critical care unit stay) and requiring a low bleeding risk invasive procedure will be considered for the trial. Once a patient has been confirmed as eligible (i.e. they satisfy the inclusion and exclusion criteria), they will be randomised (see below) and the randomly allocated treatment commenced as soon as possible. Prior to an invasive procedure, eligible patients will be randomised to one of five platelet thresholds below which they will receive a single adult equivalent dose (AED) of platelet transfusion for the index procedure and subsequent procedures during their critical care unit stay. The thresholds are:- 1. Platelet count <50 x 10e9/L 2. Platelet count<40 x 10e9/L 3. Platelet count <30 x 10e9/L 4. Platelet count <20 x 10e9/L 5. Platelet count <10 x 10e9/L Patients will be given a platelet transfusion prior to the invasive procedure if their platelet count is below the threshold to which they have been allocated. Patients remain in their allocated ‘group’ (threshold) for the duration of their critical care unit stay. In all groups, all other treatments and procedures will be carried out in accordance with standard NHS care and local practice. CONSENT As eligible patients will be critically ill at the point in which they become eligible for T4P – a model of research without prior consent (RWPC) (also known as 'deferred consent') is proposed. This model is believed to be the most appropriate as low bleeding risk interventional procedures are often initiated as a life-saving measure, during an emergency clinical situation. Patients will lack mental capacity due to their medical condition and by virtue of serious illness that required admission to a critical care unit (or continuing treatment in critical care) at the point that they become eligible for the trial. Any delay in commencing the trial treatment could be detrimental to the patient, as well as to the scientific validity of the trial. In brief, once a patient is screened as eligible for the trial (i.e. satisfies inclusion and exclusion criteria), they will be enrolled and randomised to receive the assigned treatment immediately. Patients in critical care units are monitored very closely and clinical/research staff working in this setting have extensive experience of assessing capacity in their patients. For patients recruited in England, Wales and Northern Ireland, once a patient has regained capacity, they will be approached by an authorised member of the site research team for informed deferred consent. This will be done as soon as practically possible (usually within 24 - 48 hours of the patient regaining capacity). In the interim period - once the patient’s medical situation is deemed to no longer be an emergency, a Personal Consultee will be approached (in person or by telephone) to provide their opinion of the patient’s wishes regarding participating in the trial. Telephone and postal mechanisms for consent is also in place for the situation where patients are discharged from hospital prior to confirming their consent decision. This type of consent model is used in clinical trials comparing treatments in emergency clinical situations (such as this one) to find out which is best. The specific model proposed for T4P has been informed/approved by our Patient and Public Involvement (PPI) co-investigator. For patients recruited in Scotland, consent must be in place prior to randomisation. This can be sought from the patient, or if they lack capacity, from a Personal Legal Representative. If consent sought from a Personal Legal Representative prior to randomisation, consent will then be sought after randomisation from the patient when they regain capacity. This consent model in Scotland has been reviewed and approved by Scotland A REC and is in accordance with the Adults with Incapacity (Scotland) Act 2000. At 90 days and 1 year, participants will be posted questionnaires about health-related quality of life and their use of health services since leaving hospital. These questionnaires have been used in previous critical care unit trials and will provide valuable information for the integrated economic evaluation. The questionnaires are designed to take no longer than 15 minutes to complete. A stamped addressed envelope and a pen will be included, so it will not cost the patient anything. A trained member of the T4P team at the ICNARC CTU will telephone participants who have not returned the questionnaire after three weeks, to check if they have received it and offer the option of resending the questionnaire (either by post or email) or going through the questionnaire over the telephone. INTERNAL PILOT The pilot phase will cover the first 12 months of recruitment, assessing recruitment, willingness to randomise, protocol adherence and data quality. Data will be analysed at the end of the internal pilot trial stage. The analysis will take place in month 20 of the trial to allow data to be collected and entered to assess all progression criteria. The outcome of this analysis will be presented to the majority-independent Trial Steering Committee who will provide their recommendation as to whether the trial should continue to the Funder (National Institute for Health Research (NIHR), Health Technology Assessment (HTA) Programme). The final decision on progression from the pilot stage to the full trial will be made by the NIHR HTA programme after recommendation by the TSC. INDEPENDENT COMMITTEES Both a Trial Steering Committee and an independent Data Monitoring & Ethics Committee (DMEC) will be convened and will meet regularly during the trial. The DMEC will monitor recruitment and retention, protocol adherence (including adherence to treatment protocols) and patient safety (including serious adverse events), and will review the interim analysis. TIMELINE Months 1-6: Study set-up: all approvals & preparation for the start of the trial (site sign-up and local approvals, production of materials for participating sites, conduct site initiation meetings) Months 7-48 : Recruitment/follow-up period Months 7-18: Internal pilot stage Month 16: First annual REC report Month 19: First follow-up questionnaires sent Month 20: Second DMEC and TSC meetings to review internal pilot analysis Internal pilot report submitted to NIHR HTA Month 48: Close to recruitment Month 52: Final follow-up questionnaires Months 48-60: Analysis and dissemination Month 53: Database lock for primary analysis (clinical and economic evaluation) Commence primary analysis and write up Month 55: Lock database for longer-term outcomes Month 59: Submit primary outcome paper Collaborators’ meeting Final DMEC and TSC meetings Month 60: Submit longer-term outcomes paper and draft final report to NIHR Previous interventions: T4P is a large-scale, multi-centre, data-enabled, registry-embedded, open-label, randomised, comparative effectiveness trial with an internal pilot across five equally spaced platelet count thresholds (<10 - <50 x 10e9/L). There will be an integrated economic evaluation. The trial plans to include 2550 critically ill patients recruited from 66 NHS adult critical care units over a period of 42 months. The normal platelet count is 150-450 x 10e9/L. Patients whose platelet count is below 50 x 10e9/L (at any time in their critical care unit stay) and requiring a low bleeding risk invasive procedure will be considered for the trial. Once a patient has been confirmed as eligible (i.e. they satisfy the inclusion and exclusion criteria), they will be randomised (see below) and the randomly allocated treatment commenced as soon as possible. Prior to an invasive procedure, eligible patients will be randomised to one of five platelet thresholds below which they will receive a single adult equivalent dose (AED) of platelet transfusion for the index procedure and subsequent procedures during their critical care unit stay. The thresholds are:- 1. Platelet count <50 x 10e9/L 2. Platelet count<40 x 10e9/L 3. Platelet count <30 x 10e9/L 4. Platelet count <20 x 10e9/L 5. Platelet count <10 x 10e9/L Patients will be given a platelet transfusion prior to the invasive procedure if their platelet count is below the threshold to which they have been allocated. Patients remain in their allocated ‘group’ (threshold) for the duration of their critical care unit stay. In all groups, all other treatments and procedures will be carried out in accordance with standard NHS care and local practice. CONSENT As eligible patients will be critically ill at the point in which they become eligible for T4P – a model of research without prior consent (RWPC) (also known as 'deferred consent') is proposed. This model is believed to be the most appropriate as low bleeding risk interventional procedures are often initiated as a life-saving measure, during an emergency clinical situation. Patients will lack mental capacity due to their medical condition and by virtue of serious illness that required admission to a critical care unit (or continuing treatment in critical care) at the point that they become eligible for the trial. Any delay in commencing the trial treatment could be detrimental to the patient, as well as to the scientific validity of the trial. In brief, once a patient is screened as eligible for the trial (i.e. satisfies inclusion and exclusion criteria), they will be enrolled and randomised to receive the assigned treatment immediately. Patients in critical care units are monitored very closely and clinical/research staff working in this setting have extensive experience of assessing capacity in their patients. Once a patient has regained capacity, they will be approached by an authorised member of the site research team for informed deferred consent. This will be done as soon as practically possible (usually within 24 - 48 hours of the patient regaining capacity). In the interim period - once the patient’s medical situation is deemed to no longer be an emergency, a Personal Consultee will be approached (in person or by telephone) to provide their opinion of the patient’s wishes regarding participating in the trial. Telephone and postal mechanisms for consent is also in place for the situation where patients are discharged from hospital prior to confirming their consent decision. This type of consent model is used in clinical trials comparing treatments in emergency clinical situations (such as this one) to find out which is best. The specific model proposed for T4P has been informed/approved by our Patient and Public Involvement (PPI) co-investigator. At 90 days and 1 year, participants will be posted questionnaires about health-related quality of life and their use of health services since leaving hospital. These questionnaires have been used in previous critical care unit trials and will provide valuable information for the integrated economic evaluation. The questionnaires are designed to take no longer than 15 minutes to complete. A stamped addressed envelope and a pen will be included, so it will not cost the patient anything. A trained member of the T4P team at the ICNARC CTU will telephone participants who have not returned the questionnaire after three weeks, to check if they have received it and offer the option of resending the questionnaire (either by post or email) or going through the questionnaire over the telephone. INTERNAL PILOT The pilot phase will cover the first 12 months of recruitment, assessing recruitment, willingness to randomise, protocol adherence and data quality. Data will be analysed at the end of the internal pilot trial stage. The analysis will take place in month 20 of the trial to allow data to be collected and entered to assess all progression criteria. The outcome of this analysis will be presented to the majority-independent Trial Steering Committee who will provide their recommendation as to whether the trial should continue to the Funder (National Institute for Health Research (NIHR), Health Technology Assessment (HTA) Programme). The final decision on progression from the pilot stage to the full trial will be made by the NIHR HTA programme after recommendation by the TSC. INDEPENDENT COMMITTEES Both a Trial Steering Committee and an independent Data Monitoring & Ethics Committee (DMEC) will be convened and will meet regularly during the trial. The DMEC will monitor recruitment and retention, protocol adherence (including adherence to treatment protocols) and patient safety (including serious adverse events), and will review the interim analysis. TIMELINE Months 1-6: Study set-up: all approvals & preparation for the start of the trial (site sign-up and local approvals, production of materials for participating sites, conduct site initiation meetings) Months 7-48 : Recruitment/follow-up period Months 7-18: Internal pilot stage Month 16: First annual REC report Month 19: First follow-up questionnaires sent Month 20: Second DMEC and TSC meetings to review internal pilot analysis Internal pilot report submitted to NIHR HTA Month 48: Close to recruitment Month 52: Final follow-up questionnaires Months 48-60: Analysis and dissemination Month 53: Database lock for primary analysis (clinical and economic evaluation) Commence primary analysis and write up Month 55: Lock database for longer-term outcomes Month 59: Submit primary outcome paper Collaborators’ meeting Final DMEC and TSC meetings Month 60: Submit longer-term outcomes paper and draft final report to NIHR
Intervention type	Other
Primary outcome measure	All-cause mortality at 90 days measured through review of patient medical notes at 90 days post-randomisation and/or data linkage with nationally held death registrations. Primary health economic outcome measure: Incremental costs, quality-adjusted life year (QALYs) and net monetary benefit at 90 days, measured through combining Health-related Quality of Life (EuroQol EQ-5D-5L questionnaire) data, valued resource use data obtained via a health services questionnaire and data obtained through linkage with national hospital episode statistics, death registrations and the national clinical audit for adult critical care.
Secondary outcome measures	1. Mortality at discharge from critical care unit, hospital and at 1 year, measured through review of patient medical notes at the relevant timepoints and/or data linkage with nationally held death registrations and the national clinical audit for adult critical care (for mortality at discharge) 2. Survival to longest available follow-up, measured by review of patient medical notes and/or data linkage with nationally held death registrations 3. Rates of major and fatal bleeds classified according to the HEmorhage Measurement (HEME) bleeding score, measured through review of patient medical notes up until critical care unit discharge 4. Venous and arterial thromboses in hospital and to 1 year, measured through review of patient medical notes at hospital discharge, data obtained via a health services questionnaire and through data linkage with national hospital episodes statistics and the NICE-mandated hospital-acquired venous thromboembolism (VTE) audit 5. Duration of renal, advanced cardiovascular and advanced respiratory support according to UK Critical Care Minimum Data Set (CCMDS) criteria, measured through review of patient medical notes during critical care admission and data obtained through linkage with the national clinical audit for adult critical care 6. Length of critical care unit and acute hospital stay, measured through review of patient medical notes and data obtained through linkage with the national clinical audit for adult critical care 7. Health-related quality of life measured through EQ-5D-5L questionnaire at 90 days and 1-year timepoints 8. Resource use and costs at 90 days and 1 year, measured by valuing resource use data obtained via a health services questionnaire administered to patients and through data linkage with national hospital episode statistics and the national clinical audit for adult critical care 9. Net monetary benefit (NMB) at 1 year, measured through combining health-related quality of life (EQ-5D-5L questionnaire) data, valued resource use data obtained via a health services questionnaire and data obtained through linkage with national hospital episode statistics, death registrations and the national clinical audit for adult critical care
Overall study start date	01/01/2022
Overall study end date	31/12/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 2550; UK Sample Size: 2550
Participant inclusion criteria	Current participant inclusion criteria as of 17/03/2023: 1. Adult (aged 18 years or older) 2. Accepted for admission or admitted to a participating critical care unit 3. Platelet count <50 x 10e9/l 4. Planned to undergo a specified* low bleeding risk invasive procedure OR platelet transfusion being considered for an 'other' procedure Specified low bleeding risk invasive procedures include the following: 1. Central venous vascular catheter insertion (including vascular access for renal replacement therapy) 2. Paracentesis/superficial abdominal fluid collection drainage 3. Pleural aspiration ‘Other’ procedures may be included if the clinician deems these to be a low bleeding risk invasive procedure and a platelet transfusion is being considered for the procedure. These include, but are not limited to, the following: 1. Arterial catheter insertion 2. Arterial or central venous catheter removal 3. Pleural drain 4. Interventional radiology (as defined by Society of Interventional Radiology guidelines) 5. Bronchoscopy with or without lavage 6. Wound dressing changes 7. Surgical procedures where the clinical team agree the risk of bleeding is low, e.g. re-look laparotomy, or wound closure Previous participant inclusion criteria: 1. Adult (aged 18 years or older) 2. Accepted for admission or admitted to a participating critical care unit 3. Platelet count <50 x 10e9/l 4. Platelet transfusion being considered for a low bleeding risk invasive procedure *Low bleeding risk invasive procedures include the following: 1. Vascular catheter insertion and removal (central venous – including vascular access for renal replacement therapy) 2. Paracentesis/superficial abdominal fluid collection drainage 3. Pleural aspiration ‘Other’ procedures may be included if the clinician deems these to be a low bleeding risk invasive procedure. These include, but are not limited to, the following: 1. Arterial catheter line insertion 2. Pleural drain 3. Interventional radiology (as defined by Society of Interventional Radiology guidelines) 4. Bronchoscopy with or without lavage 5. Wound dressing changes 6. Surgical procedures where the clinical team agree risk of bleeding is low, e.g. re-look laparotomy, or wound closure
Participant exclusion criteria	Current participant exclusion criteria as of 17/03/2023: 1. Ongoing major haemorrhage requiring blood products and/or surgical/radiological intervention* 2. Intercranial haemorrhage within prior 72 hours* 3. Contra-indication to platelet transfusion (such as thrombotic microangiopathies; heparin-induced thrombocytopaenia; immune thrombocytopaenia; congenital platelet function defects) 4. Acute promyelocytic leukaemia (APML) 5. Known advance decision refusing blood/blood component transfusions (e.g. Jehovah’s Witnesses) 6. Death perceived as imminent or admission for palliation 7. Previously randomised into T4P 8. Fulfilled all the inclusion criteria and none of the other exclusion criteria ≥72 hours Exclusion criteria no. 1 and 2 are dynamic, and if resolved, the patient may be reconsidered for the trial Previous participant exclusion criteria: 1. Ongoing major haemorrhage requiring blood products and/or surgical/radiological intervention 2. Intercranial haemorrhage within prior 72 hours* 3. Contra-indication to platelet transfusion (such as thrombotic microangiopathies; heparin-induced thrombocytopaenia; immune thrombocytopaenia; congenital platelet function defects) 4. Advance decision refusing blood/blood component transfusions (e.g. Jehovah’s Witnesses) 5. Death perceived as imminent or admission for palliation 6. Previously randomised into T4P 7. Fulfilled all the inclusion criteria and none of the other exclusion criteria ≥72 hours *Exclusion criteria no. 1 and 2 are dynamic, and if resolved, the patient may be reconsidered for the trial
Recruitment start date	19/10/2022
Recruitment end date	31/12/2025

Locations

Countries of recruitment

England
Scotland
United Kingdom
Wales

Study participating centres

Barnet Hospital

Wellhouse Lane
Barnet
EN5 3DJ
United Kingdom

Victoria Hospital (blackpool)

Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Chelsea & Westminster Hospital

369 Fulham Road
London
SW10 9NH
United Kingdom

Chesterfield Royal Hospital

Chesterfield Road
Calow
Chesterfield
S44 5BL
United Kingdom

Countess of Chester Hospital

Countess of Chester Health Park
Liverpool Road
Chester
CH2 1UL
United Kingdom

Croydon University Hospital

London Road
Croydon
CR7 7YE
United Kingdom

Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Great Western Hospital

Marlborough Road
Swindon
SN3 6BB
United Kingdom

Guy's and St Thomas' Hospitals

Trust Offices
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Heartlands Hospital

Bordesley Green East
Bordesley Green
Birmingham
B9 5ST
United Kingdom

Good Hope Hospital

Rectory Road
Sutton Coldfield
B75 7RR
United Kingdom

Hull Royal Infirmary

Anlaby Road
Hull
HU3 2JZ
United Kingdom

John Radcliffe Hospital

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Kettering General Hospital

Rothwell Road
Kettering
NN16 8UZ
United Kingdom

Kings College Hospital

Mapother House
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom

Kings Mill Hospital

Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom

Leicester Royal Infirmary

Infirmary Square
Leicester
LE1 5WW
United Kingdom

Liverpool Heart & Chest Hospital

Broadgreen Hospital
Thomas Drive
Liverpool
L14 3PE
United Kingdom

Milton Keynes University Hospital

Standing Way
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom

Northumbria Specialist Emergency Care Hospital

Northumbria Way
Cramlington
NE23 6NZ
United Kingdom

Pilgrim Hospital

Sibsey Road
Boston
PE21 9QS
United Kingdom

Poole Hospital

Longfleet Road
Poole
BH15 2JB
United Kingdom

University Hospital Birmingham

Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Queen Elizabeth Hospital

Woolwich Stadium Road
Woolwich
London
SE18 4QH
United Kingdom

Burton Hospital

Queens Hospital
Belvedere Road
Burton-on-trent
DE13 0RB
United Kingdom

Queens Medical Centre

Derby Road
Nottingham
NG7 2UH
United Kingdom

Nottingham City Hospital

Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Royal Berkshire Hospital

Royal Berkshire Hospital
London Road
Reading
RG1 5AN
United Kingdom

Royal Hampshire County Hospital

Romsey Road
Winchester
SO22 5DG
United Kingdom

Royal Liverpool University Hospital

Prescot Street
Liverpool
L7 8XP
United Kingdom

Royal Papworth Hospital

Papworth Road
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom

New Cross Hospital Royal Wolverhampton

Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Russells Hall Hospital

Pensnett Road
Dudley
DY1 2HQ
United Kingdom

St Georges at Mayday University Hospital

530 London Road
Thornton Heath
CR7 7YE
United Kingdom

St Richards Hospital

Spitalfield Lane
Chichester
PO19 6SE
United Kingdom

Tameside General Hospital

Fountain Street
Ashton-under-lyne
OL6 9RW
United Kingdom

Treliske Hospital

Treliske
Truro
TR1 3LJ
United Kingdom

University Hospital Coventry

Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Warrington Hospital (site)

Warrington Hospital
Lovely Lane
Warrington
WA5 1QG
United Kingdom

West Middlesex University Hospital

Twickenham Road
Isleworth
TW7 6AF
United Kingdom

Wexham Park Hospital

Wexham Street
Wexham
Slough
SL2 4HL
United Kingdom

The Whittington Hospital

Highgate Hill
London
N19 5NF
United Kingdom

Aberdeen Royal Infirmary

Foresterhill Road
Aberdeen
AB25 2ZN
United Kingdom

Western General Hospital

Crewe Road South
Edinburgh
Lothian
EH4 2XU
United Kingdom

University Hospital of North Durham

University Hospital of Durham
Dryburn Hospital
North Road
Durham
DH1 5TW
United Kingdom

Darlington Memorial Hospital NHS Trust

Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

West Cumbria Health Care NHS Trust

West Cumberland Hospital
Hensingham
Whitehaven
CA28 8JG
United Kingdom

Salford Royal Hospital

Stott Lane
Eccles
Salford
M6 8HD
United Kingdom

Fairfield General Hospital

Fairfield General Hospital
Rochdale Old Road
Bury
BL9 7TD
United Kingdom

Medway NHS Foundation Trust

Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom

Newham University Hospital NHS Trust

Newham General Hospital
Glen Road
London
E13 8SL
United Kingdom

Sponsor information

University of Oxford
University/education

Research Governance, Ethics and Assurance
Joint Research Office
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
United Kingdom

Phone	+44 (0)1865 289884
Email	ctrg@admin.ox.ac.uk
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Government

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR131822

No information available

Results and Publications

Intention to publish date	31/12/2027
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	The results of T4P will be disseminated actively and extensively. This will cover both progress during the trial period and the results at the end of the study. Outputs will include, but will not be limited to, the following areas: 1. Meeting and conference presentations (international and national) of study progress and results 2. Publication of study (1) protocol, (2) statistical analysis plan, (3) primary results, and (4) longer-term outcomes, including economic evaluation
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from T4P@icnarc.org

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version 2.0	25/11/2022	22/05/2023	No	No
HRA research summary			28/06/2023	No	No
Protocol file	version 3.1	16/01/2024	07/06/2024	No	No

Additional files

ISRCTN79371664_PROTOCOL_V2.0_25Nov22.pdf
ISRCTN79371664_PROTOCOL_V3.1_16Jan24.pdf

Editorial Notes

07/06/2024: The following changes were made to the study record:
1. Protocol uploaded.
2. The interventions were updated.
3. Scotland was added to the countries of recruitment.
4. The study participating centres were updated to remove Barnsley Hospitals, Bradford Royal Infirmary, Darent Valley Hospital, East Surrey Hospital, The Lister Hospital, Northampton General Hospital, Northwick Park Hospital, Torbay Hospital, Worcester Royal Hospital, Alexandra Hospital, Ysbyty Wrexham Maelor, Yeovil District Hospital, York Hospital, Ysbyty Gwynedd Day Hospital, and add Aberdeen Royal Infirmary, Western General Hospital, University Hospital of North Durham, Darlington Memorial Hospital NHS Trust, West Cumbria Health Care NHS Trust, Salford Royal Hospital, Fairfield General Hospital, Medway NHS Foundation Trust, Newham University Hospital NHS Trust.
22/05/2023: Protocol uploaded.
17/03/2023: The following updates have been made to the study record:
1. The participant exclusion criteria have been changed.
2. The participant inclusion criteria have been changed.
01/11/2022: The recruitment start date was changed from 03/10/2022 to 19/10/2022.
01/09/2022: Trial's existence confirmed by the NIHR.