Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06529536
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-26
Brief Title:
Utilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Genotype Informed Bayesian Dosing of Tacrolimus in Solid Organ Transplant- Pharmacogenomic Implementation in Children
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BRUNO-PIC
Brief 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
Detailed Description:
Tacrolimus a calcineurin inhibitor is an effective immunosuppressant for solid organ transplants SOT Due to its narrow therapeutic index and individual variability in its pharmacokinetics PK this can lead to inefficacy toxicities and suboptimal outcomes
Tacrolimus is typically administered orally twice daily with a starting dose scaled linearly to body weight mgkg Dose is then adjusted based on measured steady-state trough pre-dose whole blood tacrolimus concentrations to bring to within a desired therapeutic range However this dosing strategy remains associated with incomplete effectiveness and toxicities in a substantial proportion of recipients related to under- or over-exposure respectively
Cytochrome P450 CYP3A4 and CYP3A5 enzymes metabolise tacrolimus with research suggesting a link between the CYP3A5 genetic makeup and achieving tacrolimus target levels Genotyping for the CYP3A5 gene prior to SOT can identify individuals who are at risk of high or low tacrolimus levels and guide tacrolimus dosing prior to transplantation Bayesian prediction is a pharmaco-statistical technique that uses population pharmacokinetic data and individual patient characteristics to accurately predict the tacrolimus dose required to achieve a target concentration Subtherapeutic levels post-transplant increases the risk of acute rejection Furthermore failure to maintain the target tacrolimus range for the first 6 months significantly raises the chance of rejection donor-specific antibody formation and graft loss
Genotype informed dosing algorithms may optimise and ameliorate sub-therapeutic levels thus potentially reducing the risk of rejection or toxicity
To determine if implementing a genotype-informed Bayesian dosing of tacrolimus is superior to standard weight-based dosing and empiric dose adjustment to trough concentrations post SOT a combined retrospectiveprospective cohort study in Solid Organ Transplant recipients will be undertaken at The Royal Childrens Hospital Melbourne
The outcomes from the Retrospective cohort n45 using clinician-led therapeutic drug monitoring will be compared with the Prospective cohort n45 using genotype to predict initial tacrolimus doses and predictive Bayesian dosing for ongoing tacrolimus dosing over a 12-week period
Tacrolimus is typically administered orally twice daily with a starting dose scaled linearly to body weight mgkg Dose is then adjusted based on measured steady-state trough pre-dose whole blood tacrolimus concentrations to bring to within a desired therapeutic range However this dosing strategy remains associated with incomplete effectiveness and toxicities in a substantial proportion of recipients related to under- or over-exposure respectively
Cytochrome P450 CYP3A4 and CYP3A5 enzymes metabolise tacrolimus with research suggesting a link between the CYP3A5 genetic makeup and achieving tacrolimus target levels Genotyping for the CYP3A5 gene prior to SOT can identify individuals who are at risk of high or low tacrolimus levels and guide tacrolimus dosing prior to transplantation Bayesian prediction is a pharmaco-statistical technique that uses population pharmacokinetic data and individual patient characteristics to accurately predict the tacrolimus dose required to achieve a target concentration Subtherapeutic levels post-transplant increases the risk of acute rejection Furthermore failure to maintain the target tacrolimus range for the first 6 months significantly raises the chance of rejection donor-specific antibody formation and graft loss
Genotype informed dosing algorithms may optimise and ameliorate sub-therapeutic levels thus potentially reducing the risk of rejection or toxicity
To determine if implementing a genotype-informed Bayesian dosing of tacrolimus is superior to standard weight-based dosing and empiric dose adjustment to trough concentrations post SOT a combined retrospectiveprospective cohort study in Solid Organ Transplant recipients will be undertaken at The Royal Childrens Hospital Melbourne
The outcomes from the Retrospective cohort n45 using clinician-led therapeutic drug monitoring will be compared with the Prospective cohort n45 using genotype to predict initial tacrolimus doses and predictive Bayesian dosing for ongoing tacrolimus dosing over a 12-week period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None