Multicentre, controlled, randomised and single-blind, adaptive phase IV protocol to evaluate effectiveness and cost-effectiveness of a pre-emptive genotyping strategy to optimise tacrolimus dosage in a pretransplant chronic kidney disease population cohort: iPHARMGx TRANSPGx nested clinical trial.

INTRODUCTION: Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as tacrolimus, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policymakers. The iPHARMGx Consortium addresses this by developing the TRANSPGx clinical trial to assess the hypothesis that widespread adoption of a pre-emptive genotyping scheme in populations susceptible to receiving tacrolimus as immunosuppressive therapy following a kidney transplant is effective, cost-effective and feasible within the Spanish National Health System (SNHS) when compared to the standard of care tacrolimus dosing.

METHODS AND ANALYSIS: The TRANSPGx trial is a multicentre, adaptive, randomised, controlled, pragmatic phase IV clinical trial nested within the iPHARMGx master protocol, with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach, with stratification by centre. After inclusion in the trial and completion of genotyping, subjects will be randomly allocated to either the experimental group (pharmacogenetic genotype-guided tacrolimus prescription) or the standard of care tacrolimus prescription (as deemed by the attending physician). The primary objective is to assess the effectiveness of a tacrolimus pre-emptive genotyping strategy in reaching tacrolimus target plasma concentrations after renal transplant. A total of 114 subjects will be recruited among the different participating centres, provided that no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period, and subjects will be followed for a 6-month period.

ETHICS AND DISSEMINATION: The TRANSPGx trial received ethical approval on 16 January 2025 (La Paz University Hospital 2024.740). Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication. Trial registration of this study can be located at both the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. The EU Clinical Trials Register is a primary registry according to the WHO.

TRIAL REGISTRATION NUMBER: EU CT number: 2024-5 16 596-32-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06701825. Protocol V. 1.2, 8 January 2025.