The OPTIMAL trial: do older adults with kidney transplants benefit from lower doses of anti-rejection tablets?
| ISRCTN | ISRCTN14416006 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14416006 |
| IRAS number | 318534 |
| Secondary identifying numbers | 5501, CPMS 53563 |
- Submission date
- 26/09/2024
- Registration date
- 09/07/2025
- Last edited
- 11/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Every day in the UK, 10 people over 65 years develop kidney failure. More of these older adults are receiving kidney transplants. People with transplants need to take tablets to prevent their bodies from rejecting the transplant (immunosuppression).
The immune system becomes less effective in later life, meaning lower doses of immunosuppression tablets may be enough to stop transplant rejection. The amount of immunosuppression medication given to older transplant recipients is based on research in young people. Immunosuppression tablets affect older adults differently, causing more infections, cancers and side effects which prevent people from living well. Lower doses of immunosuppressives may prevent these problems.
However, less immunosuppression could mean someone is more likely to need treatment for rejection. Older adults could find the side effects of treatment for rejection more severe than younger adults. It may be that older recipients prefer to live with the side effects of standard immunosuppressive doses to avoid rejection.
We do not know what the right level of immunosuppression is for older transplant recipients. There are no national guidelines. Older people cared for at different UK kidney units receive different treatments. This study aims to investigate whether lower immunosuppression drug doses are better for older transplant recipients than standard doses.
Who can participate?
New kidney transplant recipients aged 65 years and older
What does the study involve?
The researchers will give half of the participants higher doses of mycophenolate mofetil (MMF) (1.5 g each day) and half lower doses (1 g each day).
What are the possible benefits and risks of participating?
This ‘test’ trial will determine whether it would be possible to do the same trial on a larger scale. If this ‘test’ trial shows a larger trial is possible, the researchers will do a larger UK-wide study afterwards. The study results will help make sure that older transplant recipients get the drug treatment that enables them to live as long and as well as possible.
This is a very low-risk trial. It compares two different doses of mycophenolate mofetil (MMF), both of which are used in routine clinical practice. There is a national variation in the prescribing of MMF after kidney transplantation, with some centres prescribing MMF at 1.5 g/day or higher and some centres prescribing MMF at 1 g/day. We do not know which is associated with the best clinical outcomes and quality of life for patients. This trial is the first step to determine this. It is possible that the group allocated to the higher MMF dose may experience an increased risk of infection and more medication side effects than people on the lower dose: these are outcomes of interest that will be investigated in the trial. It is possible that the group allocated to the lower MMF dose may experience an increased risk of rejection than people on the higher dose: this outcome is being investigated in the trial. There is observational evidence to suggest that the lower dose is better tolerated, reduces the risk of infection, and carries no increased risk of rejection for older transplant recipients.
Research assessments and data collection will be undertaken at participants' routine clinical appointments to minimise the burden on participants. This study is a feasibility trial to determine the feasibility and acceptability of the trial before undertaking a full-scale trial. The parallel process evaluation qualitative interviews will mean data is collected on the acceptability of the treatments and the trial research visits.
Where is the study run from?
North Bristol NHS Trust (UK)
When is the study starting and how long is it expected to run for?
September 2024 to October 2026
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
Dr Phillippa (Pippa) Bailey, pippa.bailey@bristol.ac.uk
Contact information
Scientific, Principal Investigator
Bristol Medical School
Population Health Sciences
Canynge Hall
39 Whatley Road
Bristol
BS8 2PS
United Kingdom
| Phone | +44 (0)117 3314522 |
|---|---|
| pippa.bailey@bristol.ac.uk |
Study information
| Study design | Open randomized controlled parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | The OPTIMAL feasibility trial: OPTimising IMmunosuppression for older Adult kidney transpLant recipients |
| Study acronym | OPTIMAL |
| Study objectives | 1. To assess the feasibility of an RCT of lower dose MMF (1 g/day) versus higher dose MMF (1.5 g/day), and its acceptability to transplant recipients aged ≥65 years. If this study shows that an RCT is feasible and acceptable, this will lead to a larger RCT to determine whether reduced immunosuppression drug doses result in better outcomes for older age transplant recipients. 2. To estimate important parameters needed to design a future definitive RCT comparing a lower dose versus a higher dose of MMF in older transplant recipients. The study will determine the feasibility of undertaking a larger trial. The following criteria will be assessed: 1. Size of the eligible population 2. Recruitment, adherence (participant medication concordance and clinician adherence to the planned protocol regimen), and retention 3. Time between recruitment and receipt of treatment 4. Acceptability of the trial arms and methods to patients 5. Barriers and facilitators to participation and trial delivery |
| Ethics approval(s) |
Approved 04/04/2025, Wales Research Ethics Committee 2 (Health and Care Research Wales, Castlebridge 5, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922941119, +44 (0)2922 940959; Wales.REC2@wales.nhs.uk), ref: 24/WA/0343 |
| Health condition(s) or problem(s) studied | Kidney transplantation |
| Intervention | For the first 3 months following kidney transplantation, participants will be randomised to: Trial arm 1: Mycophenolate mofetil (MMF) 1 g/day OR Trial arm 2: MMF 1.5 g/day Participants in both arms will receive tacrolimus (target trough 5-8 μg/L) and prednisolone (local protocol). Randomisation of eligible individuals with concealed allocation will be undertaken using internet-based software Sealed-Envelope using minimisation. Participants will be randomised 1:1 to each trial arm, stratified by site. Minimisation will be used to ensure balance in sex, transplant match grade (levels 1-4), and whether this is a participant’s first or other transplant. The researchers will use minimisation with a probability weighting of 0.8 in order to reduce predictability. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Mycophenolate mofetil (MMF) |
| Primary outcome measure | 1. Recruitment: % of those eligible and approached who consent to randomisation at invitation (assessed at invitation/baseline) 2. Adherence: % of participants concordant with allocated treatment and reason for non-concordance (assessed at 3 months) 3. Retention: % of participants who do not withdraw from trial follow-up assessments (assessed at 3 and 6 months) |
| Secondary outcome measures | 1. Size of the eligible population (n) assessed at screening 2. Acceptability of intervention and trial methods assessed through qualitative interviews at multiple timepoints not pre-specified 3. Barriers and facilitators to intervention implementation in different settings measured by time to green light at each site and time to the recruitment of the first participant. 4. Participant and healthcare professional adherence to the intervention/trial and deviation from treatment allocation assessed through medical records of received medication at 3 months, and through qualitative interviews in parallel to trial delivery at multiple timepoints not pre-specified |
| Overall study start date | 20/09/2024 |
| Completion date | 31/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Lower age limit | 65 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | Individuals aged ≥65 years at the time of deceased-donor kidney only transplantation |
| Key exclusion criteria | 1. Previous severe reaction to MMF 2. Simultaneous dual-organ transplantation (e.g., kidney and pancreas) 3. Individuals lacking the mental capacity to consent to participation 4. Immunologically incompatible transplantation 5. Use of a T-cell depleting induction agent 6. Steroid free, rapid steroid weaning or steroid sparing regimens |
| Date of first enrolment | 30/04/2025 |
| Date of final enrolment | 01/01/2026 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Hospital/treatment centre
Southmead Hospital
Bristol
BS10 5NB
England
United Kingdom
| Phone | +44 (0)1174149330 |
|---|---|
| research@nbt.nhs.uk | |
| Website | http://www.nbt.nhs.uk/ |
"ROR" |
https://ror.org/036x6gt55 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/10/2027 |
|---|---|
| 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 | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
11/07/2025: Ethics approval details added. The IRAS number was changed from 1009909 to 318534.
26/09/2024: Study's existence confirmed by the HRA.
