Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients (TacDrop)

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.

Study Overview

• Status: Completed
• Conditions: Renal Transplant Rejection
• Intervention / Treatment: Diagnostic test: Micro sampling

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.

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital - Rikshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Renal transplant recipients in the first two months after transplantation

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Only one arm in the present study	Diagnostic test: Micro sampling; Compare finger prick micro samples with venous blood samples for measuring whole blood tacrolimus concentrations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bias of micro sample tacrolimus concentrations	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	Within one dose interval of 12 hours
Relative bias of micro sample tacrolimus concentrations	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	Within one dose interval of 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
popPK Bayesian predicted tacrolimus trough concentration	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	Within one dose interval of 12 hours
PK Bayesian predicted tacrolimus AUC0-12	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	Within one dose interval of 12 hours
Tacrolimus tremor PK/PD relation	Description of the mathematical relation between measured tacrolimus blood concentrations and specific Tac tremor over a dose interval	Within one dose interval of 12 hours

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Sandoz; The Norwegian association for renal disease and transplants
• Investigators: Principal Investigator: Karsten Midtvedt, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: renal transplantation; analytical method validation; limited sampling strategy
• Other Study ID Numbers: TacDrop

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO