PRE-DX – the impact of earlier genomic testing in the treatment of breast cancer
| ISRCTN | ISRCTN14337451 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14337451 |
| IRAS number | 286636 |
| Secondary identifying numbers | IRAS 286636, CPMS 53118 |
- Submission date
- 10/08/2022
- Registration date
- 16/08/2022
- Last edited
- 18/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Background and study aims
Currently, the treatment of breast cancer patients follows a standard clinical care pathway where a biopsy (a small sample of tissue taken from the body, in this case of the cancer cells) is collected during surgery. The biopsy sample is tested using the Oncotype DX test which gives a Recurrence Score (RS) that clinicians can use to determine the need for adjuvant treatments (radiotherapy and/or chemotherapy) in addition to surgery.
This study aims to assess the impact on patient management if the Oncotype DX test is requested on a biopsy sample taken at the time of diagnosis as opposed to a sample obtained during surgery. The availability of the Oncotype DX RS score earlier in the clinical care pathway may streamline the pathway, reducing the time to start adjuvant cancer therapy, reducing the demand on health care services, and improving patient experience.
Who can participate?
The study will recruit adult men and women with newly diagnosed breast cancer who are preparing to undergo surgery as the first treatment.
What does the study involve?
Participants will be asked to provide permission to be contacted to discuss the study and provide consent to participate in the study. Participants will be allocated into two groups at random, with two of every three participants having the DX test performed on the core diagnostic biopsy (Intervention arm), and one of every three participants having it performed on the excision stage removed during surgery as per usual care (control arm). Following consent, the participant will be asked a few baseline questions and asked to complete the Hospital Anxiety and Depression Scale questionnaire. Participants will be asked to complete the survey along with a Health Resource Utilisation questionnaire at two further timepoints in the study, once following the post-operative clinic appointment and following the offer adjuvant treatment.
What are the possible benefits and risks of participating?
There is no specific benefit to the participants other than the potential to inform the future treatment pathway for early-stage breast cancer patients. As the intervention does not alter the treatment received by the patient but rather just changes the time point when the DX-test is performed. It is considered to present no additional risks beyond those presented by the treatment they will receive regardless of the study arm they are in.
Where is the study run from?
The Newcastle-upon-Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
From September 2022 to July 2024
Who is funding the study?
Genomic Health Inc. (USA)
Who is the main contact?
Dr Matthew Northgraves, Matthew.northgraves@hyms.ac.uk
Contact information
Dr Matthew Northgraves
Scientific
Scientific
Hull Health Trials Unit
University of Hull
Cottingham Road
Hull
HU6 7RX
United Kingdom
 ORCID ID |
0000-0001-9260-8643 |
|---|---|
| Phone | +44 (0)1482 463373 |
| Matthew.northgraves@hyms.ac.uk |
Mr Henry Cain
Scientific
Scientific
Level 4 Leazes Wing.
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
| ORCID ID |
0000-0001-5903-3454 |
|---|---|
| Phone | +44 191 2826192 |
| henry.cain@nhs.net |
Study information
| Study design | Randomized controlled trial |
|---|---|
| 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 | Pre-Operative Oncotype DX testing: A decision impact study |
| Study acronym | PRE-DX |
| Study hypothesis | Primary hypothesis: The availability of the RS® results from the core biopsy in the pre-operative setting streamlines the patient management pathway. Secondary hypothesis: The availability of the RS® results from the core biopsy in the pre-operative setting reduces healthcare utilisation, improves patient experience and decreases the time to the offering of adjuvant cancer therapy. |
| Ethics approval(s) |
Approved 26/07/2022, London - Surrey Research Ethics Committee (Meeting held by video-conference via Zoom, London, None available, United Kingdom; +44 (0)207 1048 088; surrey.rec@hra.nhs.uk), ref: 20/LO/0421 |
| Condition | Breast cancer |
| Intervention | Current intervention as of 02/06/2023: As of Protocol V2.1 24/03/2023: The Oncotype DX is a prognostic test applied to guide the treatment of breast cancer. The Recurrence Score (RS) result informs recommendations made to the patient regarding the requirement for adjuvant treatment. This is a study designed to compare the current standard patient pathway where the Oncotype DX test is performed in the post-operative setting on an excisional biopsy taken during surgery with performing the test in the pre-operative setting on the core biopsy taken at diagnosis. Patients will be randomly allocated in a 1:2 ratio into either the standard or intervention arm respectively. Assessment Schedule: The study visit schedule will follow routine clinical care pathways with the only additional non-routine visit being the inclusion of a telephone or video call to obtain informed consent and conduct baseline questionnaires. Clinical attendance will be scheduled by the treating clinicians according to site clinical care pathway protocols and as such, there is no visit window for any of the outlined clinical attendances. Breast Cancer patients referred to the Breast Cancer Symptomatic Clinic from either a GP or Mammogram Screening referral will be identified for study participation at the 'Pre-Diagnostic' MDT meeting. During the MDT meeting, the patient's breast cancer and disease staging will be confirmed and the patient management plan will be determined. The 'Pre-Diagnostic' MDT meeting is not a patient clinical attendance. The breast cancer patient's first clinical attendance is at the 'Diagnostic Patient Clinic Visit', within which their cancer treatment will be confirmed. Potential participants will be provided with a Participant Information Sheet (PIS) at the 'Diagnostic Patient Clinic Visit' and provided the opportunity to discuss their respective study participation. With permission, potential participants will be referred to the site research team. If any results required to confirm eligibility are outstanding (e.g. HER2) at the diagnostic clinic appointment, the patient can still be approached provided it is clear that their eligibility is dependent on any outstanding test results. The potential participant will only be approached by the site research team once eligibility is confirmed. Alternatively, the information (e.g. PIS) can be posted to the patient following the appointment along with the accompanying invitation letter to introduce them to the study ahead of eligibility being confirmed. A follow-up call with the research team will be arranged with any patients that express an interest in participation. During the call, they will be asked to provide informed consent and then complete the baseline Hospital Anxiety and Depression Scale (HADS). If the patient is due in for a routine appointment, face-to-face consenting will be permitted but the patient will not be brought in just to consent. For participants randomly allocated into the control arm, standard practice will be followed with the Oncotype DX test requested/ordered at the 'Post-Operative MDT meeting' and performed in the post-operative setting on the excision sample obtained during surgery or if core biopsy if endocrine bridging therapy has been received). The Recurrence Score is expected to be available approximately two weeks following the 'Post Operative Results Clinic'. For participants randomly allocated into the intervention arm, the Oncotype DX test will be performed on the core biopsy that was taken at the time of diagnosis. The results of the Oncotype DX test will be available to be discussed at the 'Post-Operative MDT meeting' following surgery. This discussion will support the decision-making on treatment options. Planned surgery will not be delayed if the Recurrence Score Results are unavailable and any change to the treatment recommendation will be recorded and discussed with the participants at an additional routine clinic appointment if required. In the event of the Oncotype DX test failing in either group, repeat tests will be ordered on the operative biopsy as per standard practice. Participants in both the control and intervention arm will attend a 'Post-Operative Results Clinic' following which the recommended adjuvant treatment will commence. In both arms of the study, the interpretation of the Recurrence Score result and treatment recommendation will be at the discretion of the MDT and treating clinicians following national guidelines. The number of participant-clinician interactions between the treating team and the participant from diagnosis until being offered adjuvant treatment will be collected by the clinical research team. The participants will complete the follow-up HADS and HRUQ one week following the Postoperative results clinic and following the offer of adjuvant treatment. _____ Previous intervention: As per Protocol V1.1 (27/06/2022): The Oncotype DX is a prognostic test applied to guide the treatment of breast cancer. The Recurrence Score (RS) result informs recommendations made to the patient regarding the requirement for adjuvant treatment. This is a study designed to compare the current standard patient pathway where the Oncotype DX test is performed on an excisional biopsy taken during surgery with performing the test on the core biopsy taken at diagnosis. Patients will be randomly allocated in a 1:2 ratio into either the standard or intervention arm respectively. Assessment Schedule: The study visit schedule will follow routine clinical care pathways with the only additional non-routine visit being the inclusion of a telephone or video call to obtain informed consent and conduct baseline questionnaires. Clinical attendance will be scheduled by the treating clinicians according to site clinical care pathway protocols and as such, there is no visit window for any of the outlined clinical attendances. Breast Cancer patients referred to the Breast Cancer Symptomatic Clinic from either a GP or Mammogram Screening referral will be identified for study participation at the 'Pre-Diagnostic' MDT meeting. During the MDT meeting, the patient's breast cancer and disease staging will be confirmed and the patient management plan will be determined. The 'Pre-Diagnostic' MDT meeting is not a patient clinical attendance. The breast cancer patient's first clinical attendance is at the 'Diagnostic Patient Clinic Visit', within which their cancer treatment will be confirmed. Potential participants will be provided with a Participant Information Sheet (PIS) at the 'Diagnostic Patient Clinic Visit' and provided the opportunity to discuss their respective study participation. With permission, potential participants will be referred to the site research team. A follow-up call with the research team will be arranged with any patients that express an interest in participation. During the call, they will be asked to provide informed consent and then complete the baseline Hospital Anxiety and Depression Scale (HADS). If the patient is due in for a routine appointment, face-to-face consenting will be permitted but the patient will not be brought in just to consent. For participants randomly allocated into the control arm, standard practice will be followed with the Oncotype DX test requested/ordered at the 'Post-Operative MDT meeting' and performed on the excision sample obtained during surgery (operative biopsy). The Recurrence Score will be available approximately two weeks following the 'Post Operative Results Clinic'. For participants randomly allocated into the intervention arm, the Oncotype DX test will be performed on the core biopsy that was taken at the time of diagnosis, prior to the surgical treatment of breast cancer. The results of the Oncotype DX test will be available to be discussed at the 'Post-Operative MDT meeting' following surgery. This discussion will support the decision-making on treatment options. Planned surgery will not be delayed if the Recurrence Score Results are unavailable and any change to the treatment recommendation will be recorded and discussed with the participants at an additional routine clinic appointment if required. In the event of the Oncotype DX test failing in either group, repeat tests will be ordered on the operative biopsy as per standard practice. Participants in both the control and intervention arm will attend a 'Post-Operative Results Clinic' following which the recommended adjuvant treatment will commence. In both arms of the study, the interpretation of the Recurrence Score result and treatment recommendation will be at the discretion of the MDT and treating clinicians following national guidelines. The number of participant-clinician interactions between the treating team and the participant from diagnosis until being offered adjuvant treatment will be collected by the clinical research team. The participants will complete the follow-up HADS and HRUQ one week following the Postoperative results clinic and following the offer of adjuvant treatment. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 15/08/2023: : As of Protocol 2.2 (04/07/2023): Number of participant touch points from the participant diagnosis (defined as the date of attendance at diagnostic clinic) to the offer and prescription of adjuvant cancer treatment measured using patient records at the time of the offer and prescription of adjuvant cancer treatment. Participant touch points will be defined as a participant-clinician interaction (outpatient appointment or equivalent) between the treating team and the participant. In the event of the participant declining further treatment the date of offer should be used. _____ Previous primary outcome measure as of 02/06/2023: As of Protocol 2.0 (07/02/2023): Number of participant touch points from the initial patient approach to the offer and prescription of adjuvant cancer treatment measured using patient records at the time of the offer and prescription of adjuvant cancer treatment. Participant touch points will be defined as a participant-clinician interaction (outpatient appointment or equivalent) between the treating team and the participant. In the event of the participant declining further treatment the date of offer should be used. _____ Previous primary outcome measure as of 28/11/2022: Number of participant touch points from the initial patient approach to the offer of adjuvant cancer treatment measured using patient records at the time of the offer of adjuvant cancer treatment. Participant touch points will be defined as a participant-clinician interaction (outpatient appointment or equivalent) between the treating team and the participant. _____ Previous primary outcome measures: 1. Number of participant touch points from the initial patient approach to the offer of adjuvant cancer treatment measured using patient records at the time of the offer of adjuvant cancer treatment. Participant touch points will be defined as a participant-clinician interaction (outpatient appointment or equivalent) between the treating team and the participant. 2. Anxiety and depression symptoms measured using the Hospital Anxiety and Depression Score (HADS) at baseline, following the post-surgery clinic appointment, and following the offer of adjuvant treatment 3. Healthcare resource use measured using the patient-reported Health Resource Utilisation Questionnaire (HRUQ) completed following the post-surgery clinic appointment and following the offer of adjuvant treatment |
| Secondary outcome measures | Current secondary outcome measures as of 15/08/2023: As of Protocol 2.2 (04/07/2023): 1. Time in days between the participant diagnosis (defined as the date of attendance at diagnostic clinic) and the offer and prescription of adjuvant cancer treatment (chemotherapy, radiotherapy or endocrine therapy) 2. Time in days between the participant diagnosis (defined as the date of attendance at diagnostic clinic) and the start of the first adjuvant cancer treatment (chemotherapy, radiotherapy or endocrine therapy) 3. Alteration in the recommended treatment sequence. This is measured when a participant in the intervention arm receives neo-adjuvant treatment as the result of the Recurrence Score (RS) results from the core biopsy rather than proceeding directly to surgery. 4. Anxiety and depression symptoms measured using the Hospital Anxiety and Depression Score (HADS) at baseline, following the post-surgery clinic appointment, and following the offer of adjuvant treatment 5. Healthcare resource use measured using the patient-reported Health Resource Utilisation Questionnaire (HRUQ) completed following the post-surgery clinic appointment and following the offer of adjuvant treatment 6. Rate of failure of the Oncotype DX® assay (RS result cannot be issued) on diagnostic core biopsy specimen. This will be measured when a test on the diagnostic core biopsy specimen fails. _____ Previous secondary outcome measures as of 02/06/2023: As of Protocol 2.0 (07/02/2023): 1. Time in days between the participant diagnosis (defined as the date of attendance at diagnostic clinic) and the offer and prescription of adjuvant cancer treatment (chemotherapy, radiotherapy or endocrine therapy) 2. Alteration in the recommended treatment sequence. This is measured when a participant in the intervention arm receives neo-adjuvant treatment as the result of the Recurrence Score (RS) results from the core biopsy rather than proceeding directly to surgery. 3. Anxiety and depression symptoms measured using the Hospital Anxiety and Depression Score (HADS) at baseline, following the post-surgery clinic appointment, and following the offer of adjuvant treatment 4. Healthcare resource use measured using the patient-reported Health Resource Utilisation Questionnaire (HRUQ) completed following the post-surgery clinic appointment and following the offer of adjuvant treatment 5. Rate of failure of the Oncotype DX® assay (RS result cannot be issued) on diagnostic core biopsy specimen. This will be measured when a test on the diagnostic core biopsy specimen fails. _____ Previous secondary outcome measures as of 28/11/2022: 1. Time in days between the participant diagnosis (defined as the date of attendance at diagnostic clinic) and the start of adjuvant cancer treatment (chemotherapy, radiotherapy or endocrine therapy) 2. Alteration in the recommended treatment sequence. This is measured when a participant in the intervention arm receives neo-adjuvant treatment as the result of the Recurrence Score (RS) results from the core biopsy rather than proceeding directly to surgery. 3. Anxiety and depression symptoms measured using the Hospital Anxiety and Depression Score (HADS) at baseline, following the post-surgery clinic appointment, and following the offer of adjuvant treatment 4. Healthcare resource use measured using the patient-reported Health Resource Utilisation Questionnaire (HRUQ) completed following the post-surgery clinic appointment and following the offer of adjuvant treatment 5. Rate of failure of the Oncotype DX® assay (RS result cannot be issued) on diagnostic core biopsy specimen. This will be measured when a test on the diagnostic core biopsy specimen fails. _____ Previous secondary outcome measure: There are no secondary outcome measures |
| Overall study start date | 01/07/2022 |
| Overall study end date | 23/11/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 330; UK Sample Size: 330 |
| Total final enrolment | 341 |
| Participant inclusion criteria | Current inclusion criteria as of 02/06/2023: As of Protocol 2.1 (24/03/2023): 1. Aged ≥18 years 2. Oestrogen receptor positive HER2-negative invasive early-stage breast cancer confirmed on diagnostic core biopsy, as per definition of hormone receptor status in NICE DG34 guidance 3. Pre-operative staging of grade 2 cancer ≥ 20 mm on all imaging modalities or grade 3 cancer of any size and N0 on axillary staging or any size or grade which is N1 on preoperative axillary ultrasound scan +/- FNA or core biopsy (If local reimbursement available for N1 patients oncotype) 3. Surgery planned as first definitive treatment 4. Fit for adjuvant chemotherapy 5. Able to provide written or remote (eConsent or postal) informed consent 6. Able to complete questionnaires and study assessments Participants receiving endocrine bridging therapy are eligible for the study provided the reason is due to a delay in planned surgery rather than for the purpose of downstaging the tumour. _____ Previous inclusion criteria: As per Protocol V1.1 (27/06/2022): 1. Aged ≥18 years 2. Oestrogen receptor positive HER2 negative invasive early stage breast cancer confirmed on diagnostic core biopsy, as per definition of hormone receptor status in NICE DG34 guidance 3. Pre-operative staging of grade 2 cancer >20 mm, or any grade 3 cancer >10 mm on all imaging modalities. N0 on axillary staging, or any size or grade which is N1 on preoperative axillary ultrasound scan +/- FNA or core biopsy (If local reimbursement available for N1 patients oncotype). 3. Surgery planned as first definitive treatment 4. Fit for adjuvant chemotherapy 5. Able to provide written or remote (eConsent or postal) informed consent 6. Able to complete questionnaires and study assessments |
| Participant exclusion criteria | 1. ER negative or HER2 positive breast cancer 2. Grade 4 or N2 disease on pre-operative staging 3. Planned for neo-adjuvant systemic therapy 4. Unfit for surgical treatment or systemic chemotherapy 5. Are unable to provide informed consent 6. Have co-existing malignant disease only if this would affect the study in the investigator’s opinion 7. Are unable to complete study questionnaires even with the assistance of the study nurse 8. Are already participating in another clinical trial |
| Recruitment start date | 10/10/2022 |
| Recruitment end date | 01/12/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Royal Liverpool University Hospital NHS Trust
Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Gateshead Health NHS Foundation Trust
Queen Elizabeth Hospital
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom
Aneurin Bevan University Lhb
Headquarters - St Cadoc's Hospital
Lodge Road
Caerleon
Newport
NP18 3XQ
United Kingdom
Lodge Road
Caerleon
Newport
NP18 3XQ
United Kingdom
The Shrewsbury and Telford Hospital NHS Trust
Mytton Oak Road
Shrewsbury
SY3 8XQ
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
Hywel Dda University Lhb
Corporate Offices, Ystwyth Building
Hafan Derwen
St Davids Park, Jobswell Road
Carmarthen
SA31 3BB
United Kingdom
Hafan Derwen
St Davids Park, Jobswell Road
Carmarthen
SA31 3BB
United Kingdom
NHS Grampian
Summerfield House
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
Hull University Teaching Hospitals NHS Trust
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Chesterfield Royal Hospital NHS Foundation Trust
Chesterfield Road
Calow
Chesterfield
S44 5BL
United Kingdom
Calow
Chesterfield
S44 5BL
United Kingdom
Wirral University Teaching Hospital NHS Foundation Trust
Arrowe Park Hospital
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Mid and South Essex NHS Foundation Trust
Prittlewell Chase
Westcliff-on-sea
SS0 0RY
United Kingdom
Westcliff-on-sea
SS0 0RY
United Kingdom
Nottingham University Hospitals NHS Trust - City Campus
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Mid Yorkshire Teaching NHS Trust
Pinderfields Hospital
Aberford Road
Wakefield
WF1 4DG
United Kingdom
Aberford Road
Wakefield
WF1 4DG
United Kingdom
North Tees and Hartlepool Ft
Hardwick Road
Stockton-on-tees
TS19 8PE
United Kingdom
Stockton-on-tees
TS19 8PE
United Kingdom
Airedale NHS Trust
Airedale General Hospital
Skipton Road
Steeton
Keighley
BD20 6TD
United Kingdom
Skipton Road
Steeton
Keighley
BD20 6TD
United Kingdom
North Cumbria University Hospitals NHS Trust
Cumberland Infirmary
Newtown Road
Carlisle
CA2 7HY
United Kingdom
Newtown Road
Carlisle
CA2 7HY
United Kingdom
Sponsor information
Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
Level 1, Regent Point
Regent Farm Road
Gosforth
Newcastle-upon-Tyne
NE3 3HD
England
United Kingdom
| Phone | +44 (0)191 2824520 |
|---|---|
| tnu-tr.sponsormanagement@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Industry
Genomic Health
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Genomic Health Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/07/2025 |
|---|---|
| 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 study team plan to disseminate trial results through publication of findings in a high impact peer-reviewed scientific journal and conference presentations. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 15/03/2024 | 18/03/2024 | Yes | No |
Editorial Notes
18/03/2024: Publication reference added.
07/12/2023: The following changes were made:
1. The total final enrolment was added.
2. The recruitment end date was changed from 01/07/2024 to 23/11/2023.
15/08/2023: The following changes were made to the trial record:
1. The primary outcome measure was changed.
2. The secondary outcome measures were changed.
3. The recruitment end date was changed from 01/09/2023 to 01/12/2023.
4. The study participating centre University Hospital of Hartlepool was removed and Hywel Dda University Lhb, NHS Grampian, Hull University Teaching Hospitals NHS Trust, Chesterfield Royal Hospital NHS Foundation Trust, Wirral University Teaching Hospital NHS Foundation Trust, Mid and South Essex NHS Foundation Trust, Nottingham University Hospitals NHS Trust - City Campus, Mid Yorkshire Teaching NHS Trust, North Tees and Hartlepool Ft, Airedale NHS Trust, North Cumbria University Hospitals NHS Trust were added.
02/06/2023: The following changes have been made:
1. The intervention has been changed.
2. The primary outcome measure has been changed.
3. The secondary outcome measures have been changed.
4. The participant inclusion criteria have been changed.
5. The recruitment end date has been changed from 02/06/2023 to 01/09/2023.
28/11/2022: The following changes have been made:
1. The primary outcome measures have been changed.
2. The secondary outcome measures have been changed.
3. Royal Liverpool University Hospital, University Hospital of Hartlepool, Oxford University Hospitals, Gateshead Health NHS Foundation Trust, Aneurin Bevan University Lhb and The Shrewsbury and Telford Hospital NHS Trust have been added as trial participating centres and United Kingdom - Wales was added to the countries of recruitment.
14/10/2022: The recruitment start date was changed from 03/10/2022 to 10/10/2022.
08/09/2022: Internal review.
10/08/2022: Trial’s existence confirmed by the National Institute for Health and Care Research.
