OPTimising IMmunosuppression for older Adult kidney transpLant recipients (the OPTIMAL Trial): a feasibility study

Research Question Is a trial of reduced immunosuppression for older adult kidney transplant recipients feasible?

Background More than 3,800 adults aged ≥65-years develop kidney failure in the UK each year; this number is increasing as the population ages.

For most people with kidney failure, a kidney transplant offers the best outcomes in terms of life-expectancy and quality of life.

However, older adults are often excluded from transplant research; therefore, the optimal immunosuppressant regimen in older adult transplant recipients is unknown. There are no national guidelines, and older patients at different UK kidney units receive different treatments. Recent systematic reviews have concluded that randomised controlled trials (RCTs) are urgently needed.

Changes to the immune system with ageing (immunosenescence) may mean that older adults have a lower risk of transplant rejection than younger adults, but higher risks of infection and malignancy.

Age-related changes can also alter the metabolism of medications, meaning older adults may be more likely to experience side effects with standard immunosuppressive regimens.

The immunosuppressant drug mycophenolate mofetil (MMF), one of three main drugs prescribed after transplant, is particularly poorly tolerated. Lower immunosuppressant doses may prevent these problems. However, less immunosuppression could mean someone is more likely to need treatment for rejection. Older adults may find the effects of treatment for rejection more severe than younger adults.

It may be that older recipients prefer to live with the risks and side-effects of standard immunosuppressants doses to avoid rejection.

Aims and Objectives The planned programme of research aims to investigate whether lower doses of MMF are associated with better clinical outcomes and quality of life in kidney transplant recipients ≥65-years. The primary aim of this study is to determine the feasibility of undertaking a pragmatic effectiveness RCT.

It will determine: the feasibility of an RCT comparing two MMF doses the acceptability of the intervention arms and trial methods to patients and clinicians estimates of important parameters needed to design a definitive RCT barriers and facilitators to the success of a future RCT Methods We will undertake a pragmatic, multi-centre randomised controlled feasibility trial comparing higher dose MMF (1.5g/day) with lower dose MMF (1g/day) in individuals aged ≥65-years at the time of kidney transplantation.

The following criteria will be assessed: size of the eligible population recruitment, adherence (participant medication concordance and clinician adherence to the planned protocol regimen), and retention acceptability of the treatment arms and trial methods to patients barriers and facilitators to participation and trial delivery.

Timelines The study will take 24 months. After ethical approval and site set-up, recruitment will occur at four hospitals over 13 months. Findings will be prepared for dissemination in the last 3 months.

Impact and Dissemination We will determine the feasibility of a definitive RCT and, if feasible, findings will inform trial design.

Findings from a definitive trial will inform clinical practice guidelines to ensure older adults receive immunosuppressants at doses that help them to live well after transplantation. Lower immunosuppressant doses may be associated with a cost-reduction for the NHS.