Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients
- Conditions
- Renal Transplant Rejection
- Interventions
- Diagnostic Test: Micro sampling
- Registration Number
- NCT03512431
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
Repeated 12-hour pharmacokinetic (PK) investigations in renal transplant recipients for parallel sampling of standard venous bloods samples and finger prick micro samples (Mitra tips). Primary aim to validate the micro sampling tacrolimus concentrations against venous blood concentrations.
- Detailed Description
Renal transplant recipients using Prograf® as part of their immunosuppressive regimen will be included in the study. Patients will receive oral and written study information and sign the informed consent before entering the study. A 12-hour pharmacokinetic investigation will be performed when Tac doses have been stable for at least 7 days (approximately 3-4 weeks posttransplant). They will continue on unchanged doses of tacrolimus as before PK investigation 1 (PK1). After at least another 7 days a second 12h PK-investigation (PK2) will be performed. If Tac doses needs to be changed after PK1 and before PK2 the second PK will not be performed.
Tac doses and blood concentration obtained as part of standard follow-up of the patients will be included in a non-parametric population model to obtain individually optimal sampling times for each patient using the MMopt function in Pmetrics®. During both PK1 and PK2 the patients themselves will be instructed to take two "home sampling" micro samples (Mitra® microsampling device) just prior to the standard vacutainer samples are obtained. Both the micro- and vacutainer samples will be drawn in 2 parallel samples right after each other and one will be mailed to the laboratory via standard mail. During PK1 the sampling times will be the same and standardized for all patients; before (0h) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours after dose administration. During PK2 individually optimized sampling times based on 2, 3 and 4 samples will be determined using the MMopt function in Pmetrics and utilizing all individual dose and concentration information from before PK2, including the rich sampling during PK1. Spread over the entire study period, at least 6 real life home samplings for trough (C0) of Tac will also be performed by the patient and mailed to the hospital.
Tacrolimus induced tremor will be measured with a center-developed method utilizing infrared determined positioning (sampling ever 5 ms) of hand joints in the x-, y, z axis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- Renal transplant recipients
- Females and males
- Patients receiving tacrolimus as part of their immunosuppressive therapy (clinical decision not influenced by this study)
- Patients on concomitant drugs with known pharmacokinetic interaction with tacrolimus
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Study group Micro sampling Only one arm in the present study
- Primary Outcome Measures
Name Time Method Absolute bias of micro sample tacrolimus concentrations Within one dose interval of 12 hours absolute bias (mico- minus vacutainer sampling) over the clinical range (1 to 40 µg/L) of micro sampled, including simulated "home sampled", Tac trough concentrations
Relative bias of micro sample tacrolimus concentrations Within one dose interval of 12 hours Relative bias (mico- minus vacutainer sampling divided by vacutainer sampled) over the clinical range (1 to 40 µg/L) of micro sampled, including simulated "home sampled", Tac trough concentrations
- Secondary Outcome Measures
Name Time Method PK Bayesian predicted tacrolimus AUC0-12 Within one dose interval of 12 hours Absolute and relative predictive error of population pharmacokinetic Bayesian estimated Tac AUC0-12 based on LSS with 2, 3 and 4 individually optimal sampling times
popPK Bayesian predicted tacrolimus trough concentration Within one dose interval of 12 hours Absolute and relative predictive error of population pharmacokinetic Bayesian estimated Tac trough concentration based on LSS with 2, 3 and 4 individually optimal sampling times more than 2 hours from trough
Tacrolimus tremor PK/PD relation Within one dose interval of 12 hours Description of the mathematical relation between measured tacrolimus blood concentrations and specific Tac tremor over a dose interval
Trial Locations
- Locations (1)
Oslo University Hospital - Rikshospitalet
🇳🇴Oslo, Norway