Utilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation.
NCT Number: NCT06529536
Acronym: BRUNO-PIC
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Solid Organ Transplant
Interventions: DIAGNOSTIC_TEST: Genotyping for CYP3A4 and CYP3A5 genes|DEVICE: Use of NextDose platform|DRUG: Tacrolimus
Sponsor: Murdoch Childrens Research Institute
Sex: ALL
Age: CHILD, ADULT
Enrollment: 45
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2024-08-05
Completion Date: 2027-08-02
Locations: Royal Children's Hospital, Melbourne, Victoria, 3052, Australia

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.

Primary Outcome Measures: Co-primary outcome: proportion of cohort with tacrolimus concentration within therapeutic range in the initial 2 weeks post-transplant, To measure 1. Proportion of Tacrolimus doses within therapeutic range in the initial 2 weeks post-transplant.

* Day 4 (assessing first dose)
* Day 10 (assessing Bayesian adapted dose), Post transplantation at Day 4 and Day 10
Secondary Outcome Measures: Proportion of cohort to reach therapeutic range in the immediate post-transplant period., To measure the time to therapeutic exposure in the immediate post-transplant period (first 2 weeks post transplant), Post transplantation at Week 2|Change in proportion of cohort to stay within therapeutic range post-transplant period., To measure the time within therapeutic range in the first 12-weeks post-transplant (as assessed at multiple time points). Timepoints: Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84, Post transplantation over a 12 week period at Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84.|Number of dose adjustments of tacrolimus dosing post-transplantation, To measure the number of dose adjustments of tacrolimus based on Therapeutic Drug Monitoring and/or Bayesian modelling., Post transplantation at Week 12|Number of related adverse events in participants relating to using genotype-informed Bayesian dosing within the first 12 weeks post transplant, To record any adverse events that occur relating to using genotyping and Bayesian dosing for dose prediction of tacrolimus. These include any subtherapeutic or supratherapeutic tacrolimus levels as a direct result of genotyping or Bayesian prediction., From first dose of Tacrolimus to 12 weeks post transplantation|Number of barriers in implementing genotype-informed Bayesian dosing, To record any barriers that occur in using genotyping and Bayesian dosing for dose prediction of tacrolimus. These can include any technical failures of the NextDose platform for dosing predictions or data access., From first dose of Tacrolimus to 12 weeks post transplantation|Number of unfavorable clinical outcomes, To compare of the number of unfavorable clinical outcomes: rejection, donor-specific antibody formation and toxicities between the two cohorts, From first dose of Tacrolimus to 12 weeks post transplantation