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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
114
Tacrolimus at the dosage reccomended by the "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing" based on the subjects pharmacogenetic phenotype.
Subject 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.
Hospital La Paz
Madrid, Madrid, Spain
RECRUITINGTacrolimus 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.
Time frame: 4 days
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.
Time frame: Though study completion, on average 18 months
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).
Time frame: Though study completion, on average 18 months
Rate of AE associated to treatment.
All adverse events associated to tacrolimus will be recorded during the study
Time frame: Though study completion, on average 18 months
Number and percentage of patients achieving tacrolimus target plasma concentrations at visit 4, 5 and 6.
Time frame: Week 4, 15 and 26
Healthcare expenditure related to predefined events of interest
Any costs made as a result of an AE
Time frame: Though study completion, on average 18 months
Incidence of discontinuation or treatment modification
Incidence of discontinuation or treatment modification due to lack of effective related to the drug of inclusion.
Time frame: Though study completion, on average 18 months
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