A trial to investigate the effect on overall health and functioning in patients with Lewy body dementia of memantine as an add-on treatment to a cholinesterase inhibitor
| ISRCTN | ISRCTN79794378 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN79794378 |
| EudraCT/CTIS number | 2021-003232-88 |
| IRAS number | 1004660 |
| Secondary identifying numbers | RES-20-041, IRAS 1004660, ERM ID 79783, CPMS 51602 |
- Submission date
- 30/04/2022
- Registration date
- 12/07/2022
- Last edited
- 13/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are related complex illnesses with a wide range of distressing symptoms. People with DLB/PDD have worse quality of life, more complex symptoms, higher care costs, and are more sensitive to medications than people with Alzheimer’s disease (AD).
Acetylcholinesterase Inhibitors (AChEI) are commonly used medicines that can help people with DLB/PDD by improving day to day functioning and thinking abilities. Another drug which might help is memantine, used to treat moderate to severe confusion in AD. It may help to improve memory, awareness and the ability to perform daily functions; however, it is not clear if adding memantine to AChEI is beneficial for people with DLB/PDD.
The aim of this trial is to find out if adding memantine to AChEI improves overall health and functioning for people with DLB or PDD.
COBALT is a double-blind, placebo-controlled, randomised trial to assess the clinical and cost-effectiveness of memantine compared to placebo in patients on an AChEI with DLB (COBALT-DLB) and PDD (COBALT-PDD). There are two separate COBALT trials being carried out using the same protocol, one in the UK and one in Australia. We plan to recruit a total of 372 patients and their caregivers/informants. The UK trial will recruit 300 participants from 30 sites and the Australian trial will recruit 72 participants from up to 5 sites. UK and Australian data will be combined for analysis.
Who can participate?
Patients aged 55 years or older with DLB or PDD, and their caregivers/informants.
What does the study involve?
DLB/PDD patients aged ≥55 years with a Mini Mental State Examination score of ≥8, on a stable dose of AChEI will be randomised 1:1 to memantine or placebo for 52 weeks. Both trials are identical in procedure and conduct, with the only variation being the disease group.
Participants and their caregiver/informant will complete assessments at baseline, 26 weeks (primary, secondary and exploratory outcomes) and 52 weeks (secondary and exploratory outcomes). During these visits assessments will be completed by the patient and their caregiver /informant.
What are the possible benefits and risks of participating?
Benefits:
The COBALT trial may help to improve treatment for people with DLB and PDD. The patients who participate in the trial may gain significant satisfaction from contributing and the regular contact from the local trial team.
Risks:
Memantine is well tolerated in patients with moderate to severe dementia in Alzheimer's Disease, with adverse events (AEs) reported in 10% of patients (comparable to placebo). The most frequently occurring adverse reactions are dizziness, headache, constipation, somnolence, and hypertension. Patients will undergo a titration phase in the first 4 weeks of their participation to assess how well they tolerate the IMP.
At some visits the questionnaires and memory testing may take 1-2 hours. Participants may find the questions tiring, tedious or embarrassing. Participants may choose not to answer any specific questions or do any test at any time.
We will ensure there are adequate rest breaks, however participants or their caregiver /informant can also request a break at any time. If the patient/caregiver requests an extended break, the assessments can be paused but must be resumed within 7 days of the initial visit.
Where is the study run from?
UK Trial - Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust (UK)
Australian Trial - The University of Melbourne (UoM)
When is the study starting and how long is it expected to run for?
March 2022 to March 2025
Who is funding the study?
NIHR Health Technology Assessment programme in the UK and National Health Medical Research Council in Australia.
Who is the main contact?
Sarah Dunn (UK), cobalt.study@ncl.ac.uk
Lesley Vidaurre (Australia), vidaurre.l@wehi.edu.au
Contact information
Public
1-4 Claremont Terrace
Newcastle Clinical Trial Unit
Newcastle University
Newcastle Upon Tyne
NE2 4AE
United Kingdom
| Phone | +44 191 208 2521 |
|---|---|
| cobalt.study@ncl.ac.uk |
Public
Watson/Yassi Laboratory
Department of Population Health and Immunity
Walter and Eliza Hall Institute of Medical Research (WEHI)
Parkville
-
Australia
| Vidaurre.l@wehi.edu.au |
Principal Investigator
Campus for Ageing and Vitality
Newcastle upon Tyne
NE4 5PL
United Kingdom
| Phone | +44 191 2081311 |
|---|---|
| john-paul.taylor@newcastle.ac.uk |
Principal Investigator
Walter and Eliza Hall Institute (WEHI)
Parkville
3052
Australia
| watson.r@wehi.edu.au |
Study information
| Study design | Interventional double-blind randomized parallel group placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN79794378_PIS_V4.0_01March2023.pdf |
| Scientific title | COmBining memantine And cholinesterase inhibitors in Lewy body dementia Treatment trial |
| Study acronym | COBALT |
| Study hypothesis | What is the clinical and cost effectiveness of memantine compared to placebo in patients with DLB (COBALT-DLB) and PDD (COBALT-PDD) who are being treated with an acetylcholinesterase inhibitor (donepezil, rivastigmine or galantamine)? Clinical effectiveness is determined using a global outcome scale - the Clinical Global Impression of Change (CGIC), 6 months after recruitment. Cost effectiveness will be measured using health economic indicators, in particular the Client Services Receipt Inventory which has been adapted for use specifically for the COBALT trial and looks at the participant's use of health and social care services. The secondary and exploratory objectives include determining whether active treatment with memantine vs. placebo leads to changes in: 1. Carer-based impression of global changes (using an adapted CGIC) 2. Cognitive function 3. Neuropsychiatric symptom frequency and severity 4. Quality of life and function for the patient 5. Quality of life for the care-giver 6. Long-term changes in global outcomes |
| Ethics approval(s) |
1. Approved 04/07/2022, East of England - Essex Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 (0)2071048227; essex.rec@hra.nhs.uk), ref: 22/EE/0075 2. Approved 24/05/2023, Royal Melbourne Hospital (Grattan Street, Parkville, 3050, Australia; +61 3 9342 8530; research@mh.org.au), ref: 2023.031 |
| Condition | Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) |
| Intervention | Memantine will be the Investigational Medicinal Product (IMP) for the COBALT trials. Memantine is currently licensed for the treatment of moderate to severe dementia in Alzheimer’s disease and is used off-licence in the UK for treatment of other dementias including DLB and PDD. IMP: Memantine 10mg tablets and Memantine 5mg tablets (Oral capsules). Placebo: Matched placebo tablets for memantine 5mg and 10 mg tablets will be manufactured and classed as an IMP for this trial (Oral capsules). All participants will receive an initial 4-week titration pack with clear instructions stated in the participant diary (part 1) dose instructions table. This table must be completed by the local trial team and the participant must be in receipt of the diary prior to starting the IMP. The 4-week titration schedule will start at 5mg daily in a single dose, taken in the morning. Thereafter, the dose will be increased by 5mg every week. The target dose will be 20mg/day, taken in the morning but titration will be based on tolerability and response. Potentially eligible patients will attend a screening visit during which consent will be obtained prior to any eligibility checks and the trial eligibility confirmation will be performed. This will include review of Liver and kidney function tests within the preceding 6 months. If no test results are available within this timeframe, a blood sample will be required to carry out these tests. A Mini Mental State Examination (MMSE) will be completed with the patient and a clinical diagnostic worksheet will be completed to confirm the patient’s diagnosis (Dementia with Lewy Bodies or Parkinson’s Disease Dementia). The patients will also be required to have a caregiver/informant in order to be eligible for the trial. The patient’s caregiver/informant should be a person that is in regular contact with the patient, who knows the patient well and is able to attend the trial follow-up visits as required. The caregiver/informant will complete assessments relating to the patient and themselves during the scheduled trial visits. The caregiver/informant should be identified during the screening process and is required to consent to take part in the COBALT trial. Once the patient has been consented and confirmed eligible, they will be randomised as a participant in either the COBALT – DLB or COBALT – PDD module of the trial, depending on their diagnosis confirmed at screening. For each trial module, a central, secure, web-based randomisation system with concealed allocation (Sealed Envelope – UK; REDCap – Aus)) will assign participants to active or placebo treatment in a 1:1 ratio. All participants, their caregiver/informants and site staff will be blinded to the participants treatment allocation, meaning that they will not know if the participant is receiving active or placebo treatment. The baseline assessments can be carried out once the participant has been consented, screened and randomised. This can occur at the same visit or can be scheduled for another day, within 14 days of the consent and screening visit. At baseline the primary, secondary, and exploratory outcome assessments will be conducted. IMP will be dispensed, along with the participant diary to record any adverse events, missed trial medication, visits to health care professionals and changes to concomitant medications. The participants and their caregiver/informant will also be given a participant safety card that includes information relating to their participation and emergency contact numbers for the trial team. Participants will be instructed to carry the card at all times and present it to any healthcare professional that they see during their COBALT trial participation. Following the participants initial baseline visit a number of follow up visits are required. Visit 5 (week 26) - These visits may occur at the local trial site, in the participant’s home. The primary, secondary and exploratory outcome assessments will be conducted per protocol section 7.4.2. IMP will be dispensed, IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. Visit 7 (week 52)/Early Withdrawal - These visits may occur at the local trial site, in the participant’s home. Secondary and exploratory outcomes will be conducted per protocol section 7.4.3. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications. Visit 2 (week 3), Visit 3 (week 8), Visit 4 (week 14) and Visit 6 (week 38) - These visits may occur at the local trial site, in the participant’s home or by telephone/video call. IMP adherence will be checked along with any side effects/Adverse Events and changes to the participant’s concomitant medications per protocol section 7.4.4. At visit 4 and visit 6 IMP will be dispensed to ensure a continued supply for the participant. A Resolution Call will be made to participants at week 56 (Visit 8) to document any adverse events they have experienced following the Visit 7 (week 52)/Early Withdrawal visit per protocol section 7.4.5. Participants are given the option to consent to a long-term follow up 12 months after the end of their participation in the trial. This can either be by review of the medical records or by speaking to someone from the local or central trial team, depending on what the participant agrees to. The purpose of this additional follow-up is to understand the long-term outcomes for patients with DLB and PDD following treatment with memantine. At selected Australian trial sites, participant consent will be obtained to collect and store approximately 60mL of blood for future research including for example biomarker development, genomics, transciptomics. Blood may be collected at up to 3 timepoints throughout the trial i.e. baseline, week 26 and week 52. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Memantine hydrochloride neuraxpharm 5 mg film-coated tablets, memantine Torrent 10 mg film-coated tablets |
| Primary outcome measure | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) scale at 26 and 52 weeks post baseline |
| Secondary outcome measures | COBALT-DLB and COBALT-PDD at baseline, 26 and 52 weeks: 1. Caregiver/Informant Impression of Change (C/I-CGIC) 2. Montreal Cognitive Assessment (MoCA) 3. Neuropsychiatric Inventory Plus (NPI+) 4. Quality of life: EuroQol EQ-5D 5 Level (EQ-5D-5L) - patient 5. Quality of life: EQ-5D-5L – proxy 6. Hospital and Anxiety Depression Scale (HADS) 7. Disability Assessment for Dementia (DAD) 8. Impact of memantine on motor function: The Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III (MDS UPDRS-III 9. Epworth Sleepiness Scale (ESS) 10. Client Service Receipt Inventory (CSRI) 11. Zarit Burden Interview (ZBI) - Caregiver/informant 12. WHO Quality of Life - BREF |
| Overall study start date | 15/03/2022 |
| Overall study end date | 31/03/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 55 Years |
| Sex | Both |
| Target number of participants | 372 (UK: 300, Australia: 72) |
| Participant inclusion criteria | Current inclusion criteria as of 21/12/2023: 1. Patients with a diagnosis or clinical features consistent with established consensus criteria for probable DLB or probable PDD 2. Aged ≥55 years 3. MMSE score ≥8. Evidence of mild, moderate, or moderate to severe cognitive impairment on similar global cognitive scales previously completed by their clinical care team (e.g., Addenbrooke’s Cognitive Examination, Mini-Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment) can be used to pre-screen the patient, prior to approach. 4. Receiving a stable dose of AChEI for ≥12 weeks prior to baseline, with no expected plans for dose adjustment during the trial period; dose adjustment will be allowed during the trial, if clinically indicated, following discussion with PI and, if required, the central trial team 5. If receiving any antiparkinsonian treatment, antidepressants, anxiolytics, antipsychotics, or other drugs with significant psychotropic effects then dose must be stable for a minimum of 4 weeks prior to enrolment with no expected plans for dose adjustment during the trial period. Dose adjustment will be allowed during the trial if clinically indicated and will be documented. If a change in medication with psychotropic effects is required, this decision can be made by the treating clinician (e.g., starting an antidepressant in clinic) without consultation with the CI. In some instances, the clinician may feel it is appropriate/relevant to discuss this with the PI prior to prescribing, for example, if the clinician feels that the medication change may have an impact on the trial and/or trial medication. Any changes should however be documented in the patient’s concomitant medications electronic Case Report Form (eCRF). 6. Patients who lack capacity will be required to have a personal/professional nominated representative who is able to give informed consent on the patient’s behalf 7. Females must be postmenopausal and not receiving IVF treatment or must have undergone permanent sterilisation. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 8. Patients with sufficient knowledge of the English language or support to understand the Patient Information Sheet and complete the trial assessments _____ Previous inclusion criteria: 1. Patients with a diagnosis or clinical features consistent with established consensus criteria for probable DLB or probable PDD. 2. Aged ≥50. 3. MMSE score ≥ 8.* 4. Receiving a stable dose of AChEI for ≥12 weeks prior to baseline, with no expected plans for dose adjustment during the trial period; dose adjustment will be allowed during the trial, if clinically indicated, following discussion with PI and, if required, the central trial team. 5. If receiving any antiparkinsonian treatment, antidepressants, anxiolytics, antipsychotics, or other drugs with significant psychotropic effects then dose must be stable for a minimum of 4 weeks prior to enrolment with no expected plans for dose adjustment during the trial period. † 6. Patients who lack capacity will be required to have a personal/professional nominated representative who is able to give informed consent on the patient’s behalf. 7. 7. Females must be postmenopausal and not receiving IVF treatment or must have undergone permanent sterilisation†† 8. Patients with sufficient knowledge of the English language or support to understand the Patient Information Sheet and complete the trial assessments *Evidence of mild, moderate, or moderate to severe cognitive impairment on similar global cognitive scales previously completed by their clinical care team (e.g., Addenbrooke’s Cognitive Examination, Mini-Addenbrooke’s Cognitive Examination, Montreal Cognitive Assessment) can be used to pre-screen the patient, prior to approach. †If a change in medication with psychotropic effects is required, this decision can be made by the treating clinician (e.g., starting an antidepressant in clinic) without consultation with the CI. In some instances, the clinician may feel it is appropriate/relevant to discuss this with the PI prior to prescribing, for example, if the clinician feels that the medication change may have an impact on the trial and/or trial medication. Any changes should however be documented in the patient’s concomitant medications electronic Case Report Form (eCRF). ††Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. |
| Participant exclusion criteria | 1. Atypical clinical features or course suggestive of an alternative dementia diagnosis. 2. Any clinically relevant concomitant disease that will affect ability to participate in the trial including, but not limited to, chronic renal disease stage 5, history of acute or chronic pancreatitis, epilepsy or former history of convulsions, patients with recent myocardial infarction (within last 6 months), uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension. 3. Patients with severe hepatic impairment based on known history and/or significant abnormalities identified in blood liver function tests (for example, levels in liver function tests that are 2-3 times higher than the upper limit of normal), which in the judgement of the local PI would exclude the patient from the trial.* 4. Patients taking memantine, amantadine, ketamine, or dextromethorphan. 5. Any neurological or major psychiatric diagnosis that may be contributing to cognitive impairment above and beyond that caused by the patients DLB or PDD. 6. Renally impaired patients with eGFR <35 mL/min/1.73m².† 7. Currently taking part in another clinical trial that would interfere with the outcomes of the COBALT trial. 8. If in the opinion of the investigator, the patient would be unable to comply with the trial procedures or has difficulty taking oral medications. 9. Patients without a reliable caregiver/informant. *LFTs should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. †U&Es should be repeated if they were not carried out at screening and were abnormal in the last 6 months and/or, in the judgement of the local PI, are clinically relevant to check before deciding trial entry. For example, a borderline eGRF <45 mL/min/1.73m². |
| Recruitment start date | 24/11/2022 |
| Recruitment end date | 31/05/2026 |
Locations
Countries of recruitment
- Australia
- England
- Northern Ireland
- Scotland
- United Kingdom
Study participating centres
Parkville
VIC 3052
Australia
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Monks Orchard Road
Beckenham
BR3 3BX
United Kingdom
Fulbourn Hospital
Fulbourn
Cambridge
CB21 5EF
United Kingdom
Lodge Approach
Runwell
Wickford
SS11 7XX
United Kingdom
Drayton High Road
Norwich
NR6 5BE
United Kingdom
Calmore
Southampton
SO40 2RZ
United Kingdom
Glasgow
G51 4TF
United Kingdom
Swandean
Arundel Road
Worthing
BN13 3EP
United Kingdom
Dryden Road
Exeter
EX2 5AF
United Kingdom
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Old Fulwood Road
Sheffield
S10 3TH
United Kingdom
West Park Hospital
Edward Pease Way
Darlington
DL2 2TS
United Kingdom
Beacon Technology Park
Dunmere Road
Bodmin
PL31 2QN
United Kingdom
Hayfield Road
Kirkcaldy
KY2 5AH
United Kingdom
Duncan Macmillan House
Porchester Road
Nottingham
NG3 6AA
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Randalls Road
Leatherhead
KT22 7AD
United Kingdom
London
TW11 0LX
United Kingdom
London
NW1 2PG
United Kingdom
Hermitage Lane
Maidstone
ME16 9PH
United Kingdom
Warneford Lane
Headington
Oxford
OX3 7JX
United Kingdom
Victoria Road
Shipley
BD18 3LD
United Kingdom
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Northern Care Alliance NHS Foundation Trust
Rochdale Old Road
Bury
Manchester
BL9 7TD
United Kingdom
Fazakerley
Liverpool
L9 7LJ
United Kingdom
Preston
PR2 8DW
United Kingdom
Kingsway Hospital
Kingsway
Derby
DE22 3LZ
United Kingdom
Greetwell Road
Lincoln
LN2 5QY
United Kingdom
Sponsor information
Hospital/treatment centre
Innovation and Clinical Effectiveness Department
St Nicholas Hospital
Jubilee Road
Newcastle upon Tyne
NE3 3XT
England
United Kingdom
| Phone | +44 191 2467221 |
|---|---|
| cntwsponsormanagement@cntw.nhs.uk | |
| Website | https://www.cntw.nhs.uk/ |
"ROR" |
https://ror.org/01ajv0n48 |
University/education
Office of Research, Ethics and Integrity
Research, Innovation and Commercialisation
161 Barry St
Carlton Victoria
Melbourne
3010
Australia
| Clinicaltrials-governance@unimelb.edu.au | |
| Website | http://www.unimelb.edu.au/ |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- NHMRC
- Location
- Australia
Results and Publications
| Intention to publish date | 01/04/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Conference presentation Publication on website Submission to regulatory authorities Data collection, validation and storage procedures will be harmonised between the UK and Australia trial teams, with an ethos of free data sharing between countries. Consent will be sought from all participants (at the point of trial enrolment) to transfer their de-identified data to the central trial team in the other country, for the purpose of data analysis and coding |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request. We will provide a contact in due course but this is likely to be the Chief Investigator, Professor John – Paul Taylor. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 3.0 | 29/06/2022 | 17/10/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | version 4.0 | 01/03/2023 | 27/03/2024 | No | Yes |
| Protocol file | version 6.0 | 11/07/2024 | 07/11/2024 | No | No |
Additional files
Editorial Notes
13/02/2025: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2025 to 31/03/2027.
2. The recruitment end date was changed from 28/02/2025 to 31/05/2026.
3. The study participating centres Sherwood Forest Hospitals NHS Foundation Trust, Northern Care Alliance NHS Foundation Trust, The Walton Centre NHS Foundation Trust, Lancashire and South Cumbria NHS Foundation Trust, Derbyshire Healthcare NHS Foundation Trust, United Lincolnshire Teaching Hospitals NHS Trust were added.
20/01/2025: The recruitment end date was changed from 03/01/2025 to 28/02/2025.
07/11/2024: Protocol uploaded. The recruitment end date was changed from 30/11/2024 to 03/01/2025.
11/09/2024: The recruitment end date was changed from 30/09/2024 to 30/11/2024.
04/04/2024: The ethics approval (2) was added.
27/03/2024: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2024 to 30/09/2024.
2. Imperial College Healthcare NHS Trust and Sheffield Teaching Hospitals NHS Foundation Trust were removed.
3. The patient information sheet version 4.0 was added.
21/12/2023: The following changes have been made:
1. The recruitment start date has been changed from 17/10/2022 to 24/11/2022.
2. The recruitment end date has been changed from 01/04/2024 to 31/03/2024.
3. The overall study end date has been changed from 01/04/2025 to 31/03/2025 and the plain English summary updated accordingly.
4. The participant inclusion criteria have been changed.
5. The plain English summary has been updated to reflect numbers of sites.
14/11/2023: The study participating centres Barking, Havering and Redbridge University Hospitals NHS Trust, Gloucestershire Health and Care NHS Foundation Trust, NHS Grampian, NHS Lanarkshire and York and Scarborough Teaching Hospitals NHS Foundation Trust were removed and NHS Lothian, Surrey and Borders Partnership NHS Foundation Trust, South West London and St George's Mental Health Trust, Imperial College Healthcare NHS Trust, Bradford District Care Trust, Belfast Health and Social Care Trust, Sheffield Teaching Hospitals NHS Foundation Trust were added.
17/10/2022: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The ethics approval was added.
3. The recruitment start date was changed from 01/09/2022 to 17/10/2022.
4. The trial website was added.
5. The participant level data sharing statement was added.
04/08/2022: Internal review.
04/05/2022: Trial's existence confirmed by NHS HRA.
