In kidney transplantation, immunosuppressive therapy is essential to control alloimmune reactions, prevent graft rejection and improve patient survival rates. However, commonly used drugs like tacrolimus (TAC) and mycophenolate mofetil (MMF) have a narrow therapeutic window and exhibit significant inter- and intra-individual variability in pharmacokinetics (PK) and dose-response relationships. Recent pilot studies suggest that the gut microbiome may influence this variability.

ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA) is a prospective, low-interventional, naturalistic longitudinal trial designed to identify biomarkers of TAC and MMF PK variability by examining gut microbiome changes and modulations after kidney transplantation and their link with TAC and MMF PK. Biological samples from 50 patients will be collected at nine specific timepoints pre- and post-transplantation using a rich PK and biological sampling strategy. This approach will enable the derivation of PK parameters for the investigated drugs and the creation of a biobank for future hypothesis testing.

The ENIGMA trial has received ethical approval from the European Medicines Agency (EMA). The reference number of our project is R&D/1325226 and is registered on the Clinical Trial Information System (CTIS) platform with European Union Clinical Trial number 2023–5 08 335-31-00. Results of the trial will be published in scientific journals and presented at different (inter)national conferences.

2023–5 08 335-31-00 EMA.

Shoulder osteoarthritis most commonly affects older adults, causing pain, reduced function and quality of life. Total shoulder replacements (TSRs) are indicated once other non-surgical options no longer provide adequate pain relief. Two main types of TSRs are widely used: anatomic TSR (aTSR) and reverse TSR (rTSR). It is not clear whether one TSR type provides better short- or long-term outcomes for patients, and which, if either, is more cost-effective for the National Health Service (NHS).

RAPSODI-UK is a multi-centre, pragmatic, two-parallel arm, superiority randomised controlled trial comparing the clinical- and cost-effectiveness of aTSR versus rTSR for adults aged 60+ with a primary diagnosis of osteoarthritis, an intact rotator cuff and bone stock suitable for TSR. Participants in both arms of the trial will receive usual post-operative rehabilitation. We aim to recruit 430 participants from approximately 28 NHS sites across the UK. The primary outcome is the Shoulder Pain and Disability Index (SPADI) at 2 years post-randomisation. Outcomes will be collected at 3, 6, 12, 18 and 24 months after randomisation. Secondary outcomes include the pain and function subscales of the SPADI, the Oxford Shoulder Score, health-related quality of life (EQ-5D-5L), complications, range of movement and strength, revisions and mortality. The between-group difference in the primary outcome will be derived from a constrained longitudinal data analysis model. We will also undertake a full health economic evaluation and conduct qualitative interviews to explore perceptions of acceptability of the two types of TSR and experiences of recovery with a sample of participants.

Ethics committee approval for this trial was obtained (London - Queen Square Research Ethics Committee, Rec Reference 22/LO/0617) on 4 October 2022. The results of the main trial will be submitted for publication in a peer-reviewed journal and using other professional and media outlets.

ISRCTN12216466.