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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug Tacrolimus
  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.
• Drug Tacrolimus
  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.

Primary outcome measures

• Tacrolimus concentrations levels [Time frame: 4 days]

Secondary outcome measures (6)

• Incremental cost-effectiveness ratio (ICER) [Time frame: Though study completion, on average 18 months]
• Number and percentage of patients with transplant rejection. [Time frame: Though study completion, on average 18 months]
• Rate of AE associated to treatment. [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 [Time frame: Though study completion, on average 18 months]
• Incidence of discontinuation or treatment modification [Time frame: Though study completion, on average 18 months]

Eligibility criteria

Inclusion criteria

• 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.
• Subjects must be naïve to any genotyping test of the following genes: CYP3A5.

Exclusion criteria

• 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.
• Any condition at medical discretion for which renal transplantation and/or study treatment should not be received.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital La Paz — Madrid

Publications

• Seco-Meseguer E, Stewart S, Diago-Sempere E, Jimenez C, Macias Carmona N, Fernandez Solis J, Vila Santandreu A, Valero San Cecilio R, Lopez Jimenez V, Carmona-Rodriguez M, Lopez-Fernandez LA, Imaz-Iglesia I, Garcia-Saiz MDM, Farre M, Rodriguez-Jimenez C, Sanabria-Cabrera J, Rosas-Alonso R, Garcia-Garcia I, Borobia AM; iPHARMGx study group. Multicentre, controlled, randomised and single-blind, adap PMID 42547238

Identifiers

NCT: NCT06701825 · 2024-516596-32-00 · 2024-516596-32-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗