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

NCT ID: NCT06701825

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-02
• Study Completion Date: 2026-12-31

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard of care

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.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: 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.

Dose adjusted by guidelines

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.

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Instituto de Investigación Hospital Universitario La Paz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital La Paz

Madrid, Madrid, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Alberto M. Borobia, MD, PhD

Role: CONTACT

alberto.borobia@salud.madrid.org

+34 912071466

Facility Contacts

Arturo Gomez Lopez de las Huertas, MD

Role: primary

Other Identifiers

2024-516596-32-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-516596-32-00

Identifier Type: -

Identifier Source: org_study_id