Computer Guided Doing of Tacrolimus in Renal Transplantation

Study Overview
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Brief Summary
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Dosing of tacrolimus is challenging due to the large inter-individual variation in its pharmacokinetics. The investigators have developed a pharmacokinetics population model that can be used to estimate individual doses of tacrolimus in renal transplant recipients. The model will be prospective tested in a randomized clinical trial. The hypothesis is that the computer model is superior to experienced transplant physicians in reaching and keeping the patients in the target range of tacrolimus.

Detailed Description
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Patients will be randomized to either computer or standard dosing strategies at time of transplantation or as early after transplantation as possible in case of deceased donor transplants. For patients in the computer arm the model will calculate the dose with the highest probability to reach the specified concentration target. For all concentrations a predictive error will be calculated and this will be the primary endpoint that the statistics will be calculated on. All patients will be followed for between 8 to 12 weeks post-transplant, according to center praxis.

Official Title
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Prospective Testing of Pharmacokinetic Population Models for Dosing of Transplanted Patients

Conditions
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Renal Transplantation

Intervention / Treatment
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* Other: Computer dosing
* Other: Standard dose determination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: renal transplant recipients using tacrolimus as part of their immunosuppression above 18 years signed informed consent Exclusion Criteria: no specific

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computer dosed<br>Patients for which the computer model will calculate the individual doses | Other: Computer dosing<br>* Pharmacokinetic population model for individual dose estimations of tacrolimus based on concentrations measurements and inclusion of relevant covariates<br>|
| Active Comparator: Control<br>Patients which will get their tacrolimus doses determined by experience transplant physicians | Other: Standard dose determination<br>* Tacrolimus dose determination according to trough concentrations and standard TDM at the clinic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive error (Cpred-Cobs) | Predictive error will be calculated as the computer predicted concentration minus the measured concentration over the first 8 to 12 weeks post-transplant in the computer group. The calculations will be binned into weekly assessments. | 8 to 12 weeks | 
| Reaching the target concentration | In each arm the deviation of the observed concentration front he preset target concentration will be calculated for each measured concentration. The deviations will be compared between the two arms. | 8 to 12 weeks post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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population model, pharmacokinetic, tacrolimus, therapeutic drug monitoring, individualized dosing