Clinical trial NCT03512431: Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients
Official title: Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Transplant Rejection
Keywords: analytical method validation
renal transplantation
limited sampling strategy
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Sandoz
name: The Norwegian association for renal disease and transplants
First posted: 2018-04-30
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Renal transplant recipients in the first two months after transplantation

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.

Eligibility criteria: Inclusion Criteria:

* Renal transplant recipients
* Females and males
* Patients receiving tacrolimus as part of their immunosuppressive therapy (clinical decision not influenced by this study)

Exclusion Criteria:

* Patients on concomitant drugs with known pharmacokinetic interaction with tacrolimus

Primary outcomes:
measure: Absolute bias of micro sample tacrolimus concentrations
timeFrame: Within one dose interval of 12 hours
measure: Relative bias of micro sample tacrolimus concentrations
timeFrame: Within one dose interval of 12 hours
Secondary outcomes:
measure: popPK Bayesian predicted tacrolimus trough concentration
timeFrame: Within one dose interval of 12 hours
measure: PK Bayesian predicted tacrolimus AUC0-12
timeFrame: Within one dose interval of 12 hours
measure: Tacrolimus tremor PK/PD relation
timeFrame: Within one dose interval of 12 hours
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital - Rikshospitalet
Study officials:
affiliation: Oslo University Hospital
name: Karsten Midtvedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: