Renal Transplantation
Conditions
Keywords
population model, pharmacokinetic, tacrolimus, therapeutic drug monitoring, individualized dosing
Brief summary
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
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.
Interventions
OTHERComputer dosing
Pharmacokinetic population model for individual dose estimations of tacrolimus based on concentrations measurements and inclusion of relevant covariates
OTHERStandard dose determination
Tacrolimus dose determination according to trough concentrations and standard TDM at the clinic
Sponsors
Rikshospitalet University Hospital
University of Oslo School of Pharmacy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* renal transplant recipients using tacrolimus as part of their immunosuppression * above 18 years * signed informed consent
Exclusion criteria
* no specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Predictive error (Cpred-Cobs) | 8 to 12 weeks | 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. |
| Reaching the target concentration | 8 to 12 weeks post-transplant | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Influence of CYP3A5 genotyping | 8 to 12 weeks post-transplant | The model will be run without any information about patients CYP3A5 genotype as this is not clinical praxis at our center yet. All patients will however be genotyped after the study and a model including this covariate will be used to recalculate the data and see if this model is superior to the simple model, primary by comparing predictive errors in the computer arm. |
Countries
Norway
Outcome results
None listed