Effectiveness and Cost-effectiveness of a Pre-emptive Genotyping Strategy in Patients Receiving Tacrolimus

A Multicentre, Controlled, Randomised and Single-blind, Adaptive Phase IV Protocol to Evaluate Effectiveness and Cost-effectiveness of Pre-emptive Genotyping Strategy to Optimise Tacrolimus Dosage in a Pretransplant Chronic Kidney Disease Population Cohort

This is a phase IV multicentre adaptive single-blinded randomized clinical trial to evaluate if preemptively genotyping populations at pretransplant chronic kidney disease susceptible of receiving tacrolimus therapy is effective, cost-effective, and feasible within the Spanish National Health System when compared to the current standard of care. This trial is nested within the iPHARMGx master protocol.

This is a nation-wide, multicentre, randomised, controlled, and adaptive phase IV clinical trial that aims to assess the effectiveness and cost-effective of pre-emptive pharmacogenetic testing strategies, including those impacted by genetic variants associated with adverse drug reactions (ADRs) or limited efficacy. The clinical trials will evaluate the effective and cost-effective of pre-emptive genotyping by defining a drug-gene-endpoint triad. Study subjects will be pre-emptively genotyped and, if found to have an actionable gene variant, randomly allocated to either a test group where guideline-based treatment modifications will be initiated or a control group that will be managed according to healthcare provider standard of care (SoC). Subsequently, subjects will be prospectively followed at prespecified timepoints. Detailed information on drug-gene-endpoint triads, allocation schemes, and follow-up visits will be provided in each of the subprotocols. A Data Monitoring Committee (DMC), composed of physician experts, will be appointed for each nested trial to review the data on an ongoing basis, ensuring the safety of participants and scientific validity of the study.

Inclusion Criteria:

1. Participants must be willing and able to provide written informed consent prior the initiation of any study procedures.
2. Subject or their legally authorized representative has voluntarily signed the informed consent document.
3. Participant is on the waiting list for a kidney transplant.
4. Subject is able and willing to take part and be followed-up for the majority of the study duration, and adhere to the procedures specified in this protocol.
5. Subjects must be naïve to any genotyping test of the following genes: CYP3A5.

Exclusion Criteria:

1. Known hypersensitivity/allergy reaction to tacrolimus or any of the excipients.
2. History of renal, heart, and/or liver transplant.
3. History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere in a relevant manner with the absorption, distribution, metabolism, or excretion of the study treatment, except for renal disease.
4. Any condition or situation precluding or interfering the compliance with the protocol.
5. Any condition at medical discretion for which renal transplantation and/or study treatment should not be received.