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.
Participants must be willing and able to provide written informed consent prior the initiation of any study procedures.
Subject or their legally authorized representative has voluntarily signed the informed consent document.
Participant is on the waiting list for a kidney transplant.
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.
Known hypersensitivity/allergy reaction to tacrolimus or any of the excipients.
History of renal, heart, and/or liver transplant.
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.
Any condition or situation precluding or interfering the compliance with the protocol.
Parallel
Tacrolimus
DrugTacrolimus at the dosage reccomended by the "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing" based on the subjects pharmacogenetic phenotype.
Tacrolimus
DrugSubject allocated to this arm will receive tacrolimus according to clinical practice and the drug's product labelling. These subject will not receive a personalised dose based on their pharmacogenetic phenotype.
Tacrolimus concentrations levels
Number and percentage of patients achieving tacrolimus target plasma concentrations at visit 3. Tacrolimus concentrations levels at day 4 (+/-1d) will be the effectiveness surrogate outcome. It will be considered therapeutic range levels between 7-10 ng/ml.
Incremental cost-effectiveness ratio (ICER)
Cost-effectiveness ratio that divides the differences in costs between both treatments by the difference in effectiveness between both treatments.
Number and percentage of patients with transplant rejection.
Transplant rejection will be considered if there is histological confirmation and/or the patient initiates any type of therapy aimed at treating rejection (e.g. corticosteroids).
Rate of AE associated to treatment.
All adverse events associated to tacrolimus will be recorded during the study
Number and percentage of patients achieving tacrolimus target plasma concentrations at visit 4, 5 and 6.
Novel prognostic and predictive genetic biomarkers of tacrolimus safety and effectiveness
All participants DNA sample will be susceptible of deep sequencing analysis assessed trough techniques only available at Nation Centre of Oncological Investigations (CNIO) and genome-wide association studies when applicable
Identification of new actionable genes/relevant polymorphisms within the predefined population subsets
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Instituto de Investigación Hospital Universitario La Paz
Lead sponsor
Instituto de Salud Carlos III
Collaborator
