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

NCT06701825 | Recruiting Phase 4

• 1 other identifier: 2024-516596-32-00
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Disease, Chronic; Transplant Recipient (Kidney); Immunosuppression

Keywords

Tacrolimus; Kidney transplant; Cost-effectiveness; Pharmacogenetic; Phase IV Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 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.

  4 days

Secondary Outcomes (6)

• Incremental cost-effectiveness ratio (ICER)

  Though study completion, on average 18 months

• Number and percentage of patients with transplant rejection.

  Though study completion, on average 18 months

• Rate of AE associated to treatment.

  Though study completion, on average 18 months

• Number and percentage of patients achieving tacrolimus target plasma concentrations at visit 4, 5 and 6.

  Week 4, 15 and 26

• Healthcare expenditure related to predefined events of interest

  Though study completion, on average 18 months

Other Outcomes (2)

• Novel prognostic and predictive genetic biomarkers of tacrolimus safety and effectiveness

  Though study completion, on average 18 months

• Identification of new actionable genes/relevant polymorphisms within the predefined population subsets

  Though study completion, on average 18 months

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

Patients in this control group will receive treatment with any formulation of Tacrolimus authorized and commercialized in Spain. They will be administered tacrolimus according to clinical practice and the drug's product labeling.

Drug: Tacrolimus

Dose adjusted by guidelines

EXPERIMENTAL

Participants in this experimental group will receive treatment with any formulation of Tacrolimus authorized and commercialized in Spain. They will be administered the specific dosage of tacrolimus recommended by the Clinical Pharmacogenetics Consortium's genotype guidelines, utilizing the patient's pharmacogenetic information and characteristics.

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

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.

Standard of care

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Alberto M. Borobia, MD, PhD

CONTACT

+34 912071466; alberto.borobia@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will remain blinded to arm assigned because pharmacogenetic phenotype and tacrolimus dose-guidance will only be exclusively accesible to the attending physician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase IV, multicentre, controlled, randomized, parallel and single-blind adaptive clinical trial nested within the iPHARMGx master protocol study

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 22, 2024
• Study Start: June 2, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available at the same time as the results will be published, and will be kept available to everyone without any time limit.
• Access Criteria: Data will be available indefinitely on the publisher's website, as long as it is kept by the Publisher, for anyone who wishes to access the data, for non-commercial purposes.

Locations

ES (1)