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

Phase 4

Not yet recruiting

• Conditions: Kidney Disease, Chronic; Transplant Recipient (Kidney); Immunosuppression
• Interventions: Drug: Tacrolimus

• Registration Number: NCT06701825
• Lead Sponsor: Instituto de Investigación Hospital Universitario La Paz

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.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-20
• Study First Submitted QC: 2024-11-20
• Study First Posted: 2024-11-22
• Last Update Submitted: 2024-11-28
• Last Update Posted: 2024-12-03
• Study Start: 2025-02-01
• Primary Completion: 2026-08-01
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Tacrolimus	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.
Dose adjusted by guidelines	Tacrolimus	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.

Primary Outcome Measures

Name	Time	Method
Tacrolimus concentrations levels	4 days	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.

Secondary Outcome Measures

Name	Time	Method
Incremental cost-effectiveness ratio (ICER)	Though study completion, on average 18 months	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.	Though study completion, on average 18 months	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.	Though study completion, on average 18 months	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.	Week 4, 15 and 26
Healthcare expenditure related to predefined events of interest	Though study completion, on average 18 months	Any costs made as a result of an AE
Incidence of discontinuation or treatment modification	Though study completion, on average 18 months	Incidence of discontinuation or treatment modification due to lack of effective related to the drug of inclusion.

Trial Locations

Locations (1)

Hospital La Paz; 🇪🇸 Madrid, Comunidad De Madrid, Spain