Utilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation.
Genotype Informed Bayesian Dosing of Tacrolimus in Solid Organ Transplant- Pharmacogenomic Implementation in Children
Murdoch Childrens Research Institute
45 participants
Aug 5, 2024
INTERVENTIONAL
Conditions
Summary
This study aims to evaluate the efficacy of genotype-informed Bayesian dosing of tacrolimus in optimising drug exposure among paediatric solid organ transplant recipients. By tailoring tacrolimus dosage based on individual genetic makeup and using Bayesian modeling to predict drug levels, the researchers hope to increase the likelihood of achieving therapeutic drug concentrations while minimising the risk of adverse events associated with subtherapeutic or supratherapeutic exposure.
Eligibility
Inclusion Criteria4
- Participants will be assigned to the prospective arm if treated at Royal Children's Hospital who are receiving a solid organ transplant (SOT) (excluding repeat graft in liver transplant recipients, or lung or intestinal transplant) and who will be on tacrolimus as one of the main immunosuppressants post-transplant.
- Age 1-18 years of age
- Kidney, liver or heart transplant recipients
- Participant and/or parent consent to the study (prospective arm only)
Exclusion Criteria5
- Previous liver transplant.
- Lung OR Intestinal transplant.
- Insufficient time before transplant for pharmacogenomic analysis (prospective arm only)
- Immunosuppressant regimen not containing tacrolimus immediate release product
- Known hypersensitivity to tacrolimus and/or its formulation.
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Interventions
Genotyping: Patients in the prospective (intervention) arm will undergo genotyping using Illumina's genome-wide genotyping array (Infinium Global Screening Array). Pre-transplant genotyping will test for CYP3A5 \*3, \*6, \*7, \*8 and \*9 alleles, and will test for CYP3A4\*22 only (with CYP3A4\*1 reported if no variant corresponding to \*22 was present). The determined diplotypes for CYP3A5 will be matched with predicted phenotypes using the Clinical Pharmacogenetics Implementation Consortium (CPIC®) proposed genotype-to-phenotype translation table. The assignment of the phenotype is outlined in the CPIC guidelines which will used to predict initial dose of tacrolimus. In addition, influence of CYP3A4 will be incorporated based on recent literature and interventional trials. Initial dose in BRUNO-PIC will use allometric size scaling from adult dose, with adjustment based on genotype (CYP3A4 \& CYP3A5)
NextDose platform is a forecasting tool used to predict tacrolimus dosage. It is a freely available tool and will be used in accordance with guideline. The dosing recommendations will be led by the academic pharmacist in consultation with the PI. This tool will use genotype-informed Bayesian dosing to help predict the time course of tacrolimus concentrations in the body.
Tacrolimus is administered to all patients post SOT at The Royal Children's Hospital (RCH)
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06529536