Register a trial

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06529536




Registration number
NCT06529536
Ethics application status
Date submitted
26/07/2024
Date registered
31/07/2024

Titles & IDs
Public title
Utilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation.
Scientific title
Genotype Informed Bayesian Dosing of Tacrolimus in Solid Organ Transplant- Pharmacogenomic Implementation in Children
Secondary ID [1] 0 0
2023/ETH02699
Universal Trial Number (UTN)
Trial acronym
BRUNO-PIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Organ Transplant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - Genotyping for CYP3A4 and CYP3A5 genes
Treatment: Devices - Use of NextDose platform
Treatment: Drugs - Tacrolimus

Experimental: Prospective Cohort: Pre-emptive CYP3A5 genotype combined with a Bayesian dose prediction - Planned SOT recipients where initial tacrolimus dosing will be based on genotype and subsequent doses predicted using Bayesian revised dosing using NextDose. NextDose, a web-based tool is a model-informed precision dosing software tool used to optimise dosage regimens. It uses Bayesian statistics to integrate prior drug information from a population pharmacokinetic (popPK) model, individual characteristics, and drug concentrations to provide the most accurate individual pharmacokinetic (PK) estimates. The popPK model, a mathematical-statistical model developed from real patient data, captures the drug's typical pharmacokinetics, its variability among individuals and over time, and the factors influencing this variability. By leveraging prior knowledge about a drug's PK along with individual patient data and drug concentrations, the software accurately estimates individual PK parameters with minimal drug concentration data. Tacrolimus dose, form, frequency, \& duration will be assessed


Diagnosis / Prognosis: Genotyping for CYP3A4 and CYP3A5 genes
Genotyping: Patients in the prospective (intervention) arm will undergo genotyping using Illumina's genome-wide genotyping array (Infinium Global Screening Array).

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.

Treatment: Devices: Use of NextDose platform
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.

Treatment: Drugs: Tacrolimus
Tacrolimus is administered to all patients post SOT at RCH
Intervention code [1] 0 0
Diagnosis / Prognosis
Intervention code [2] 0 0
Treatment: Devices
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Co-primary outcome: proportion of cohort with tacrolimus concentration within therapeutic range in the initial 2 weeks post-transplant
Timepoint [1] 0 0
Post transplantation at Day 4 and Day 10
Secondary outcome [1] 0 0
Proportion of cohort to reach therapeutic range in the immediate post-transplant period.
Timepoint [1] 0 0
Post transplantation at Week 2
Secondary outcome [2] 0 0
Change in proportion of cohort to stay within therapeutic range post-transplant period.
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Number of dose adjustments of tacrolimus dosing post-transplantation
Timepoint [3] 0 0
Post transplantation at Week 12
Secondary outcome [4] 0 0
Number of related adverse events in participants relating to using genotype-informed Bayesian dosing within the first 12 weeks post transplant
Timepoint [4] 0 0
From first dose of Tacrolimus to 12 weeks post transplantation
Secondary outcome [5] 0 0
Number of barriers in implementing genotype-informed Bayesian dosing
Timepoint [5] 0 0
From first dose of Tacrolimus to 12 weeks post transplantation
Secondary outcome [6] 0 0
Number of unfavorable clinical outcomes
Timepoint [6] 0 0
From first dose of Tacrolimus to 12 weeks post transplantation

Eligibility
Key inclusion criteria
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) and who will be on tacrolimus as one of the main immunosuppressants post-transplant.



* 1 to 18years old
* SOT transplant (planned or on waiting list) excluding repeat liver transplant.
* Heart OR Liver OR Renal Transplant
* Amenable to venepuncture and blood draw
* Patient and/or parent consented to the study.
Minimum age
1 Year
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* older than 18 year old
* younger than 1 year old
* Previous liver transplant.
* Lung OR Intestinal transplant.
* For prospective arm, patient has had a SOT prior to receiving genotyping results.
* Patient has a known hypersensitivity to tacrolimus and/or its formulation.
* On a slow release preparation of Tacrolimus (e.g Advagraf extended release Brand)
* Patient has a life expectancy estimated to be less than 12-weeks by the treating clinical team.
* Patient and/or parent is unable to consent to the study.
* Patient and/or parent is unwilling to take part in the study.

Study design
Purpose of the study
Other
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/08/2027
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rachel Conyers
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rachel Conyers
Address 0 0
Country 0 0
Phone 0 0
03 9936 6770
Fax 0 0
Email 0 0
pharmaco.genomics@mcri.edu.au
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The de-identified data set collected for this analysis of this study will be available six months after publication of the primary outcome. The study protocol and analysis plan will also be available. The data must be obtained from the Murdoch Children's Research Institute. Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the Study Management Group must see and approve the data analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgment and any additional costs involved must be covered. Should the Study Management Group be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognized research organisation which has approved the proposed analysis plan.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
6 months after publication of primary outcome
Available to whom?
1. Data access agreement;
2. approval by Trial Steering Committee;
3. recognized research institutions.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.melbournechildrens.com/mctc/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06529536