Pre-transplant Assessment of Tacrolimus Blood Level Concentration, as a Predictor of Tacrolimus Dose Requirements After Kidney Transplantation

June 6, 2011 updated by: Janssen-Cilag Pty Ltd

Pre-transplant Pharmacokinetics as a Predictor of the Tacrolimus Dose Requirement Post Renal Transplantation

The purpose of this study is to evaluate two groups of kidney transplant recipients, to determine the proportion of patients that achieve therapeutic blood concentrations of tacrolimus by Day 3 after transplantation. Patients in one group will be treated with tacrolimus according current clinical practice. The other group will have a pre-transplant assessment of their tacrolimus blood level concentration that will be used to guide post-transplantation tacrolimus dosing. Tacrolimus is a medicine that slows down the body's immune system. For this reason, it works as an anti-rejection medicine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a multicentre, open-label, prospective, 2-arm, phase IV study of tacrolimus in renal transplant recipients. Patients will be randomized to receive current clinical practice or to have a pre-transplant pharmacokinetic assessment of tacrolimus metabolism that will be used to guide post-transplantation tacrolimus dosing, with the aim of increasing the proportion of patients that achieve a tacrolimus whole blood trough level of >10 ng/mL by Day 3 post-transplantation. Patients randomized to Group 1 will take a single dose of tacrolimus (0.1 mg/kg) prior to transplantation and a blood sample will be taken to determine tacrolimus whole blood concentration at 2 hours post-dose. The result of this blood sample will be used to guide tacrolimus dosing post-transplantation. Patients that return a low tacrolimus blood concentration will have a post-transplantation starting dose of up to 0.3 mg/kg/day, whereas patients that return a high tacrolimus blood concentration will have a post-transplantation starting dose of 0.1 mg/kg/day. Patients randomized to Group 2 will also receive a single pre-operative dose of tacrolimus, but will not have their tacrolimus whole blood concentration measured at 2 hours post-dose. These patients will be managed as per standard care.

The primary objective of the trial is to compare, between the two groups, the proportion of patients that achieve a tacrolimus whole blood trough concentration of ³10 ng/mL by Day 3 post-transplantation. The hypothesis is that performing a tacrolimus whole blood concentration assessment 2 hours after a pre-operative dose (to guide tacrolimus dosing post-transplantation), will lead to an increase in the numbers of patients that achieve therapeutic blood concentrations post-transplant. The tacrolimus whole blood concentration at Day 3 post-transplantation is a marker of the risk of rejection and toxicity.

A substudy is being conducted which seeks to examine and compare clinical variability in absorption profile by measurement of the phenotype (blood levels) in kidney transplant recipients and determine the nature and extent of relationship with MDR-1 genotype, thus allowing the most predictive and cost effective method of determining tacrolimus dosing.

Pre-transplant: One single tacrolimus dose 0.1 mg/kg/day orally. Post-transplant: 0.15 - 0.3 mg/kg/day as two divided tacrolimus doses orally, the actual dose to be guided by the pre-transplant tacrolimus blood concentration.

Study Type

Interventional

Enrollment (Actual)

89

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient has end-stage kidney disease and is a suitable candidate for primary renal transplantation or re-transplantation
  • Patient is receiving a kidney transplant from a cadaveric or living (not HLA identical) donor, at least 10 years of age, with compatible ABO blood type

Exclusion Criteria:

  • Patients receiving a graft from a non-heart-beating donor
  • known to have significant liver disease, or is receiving a graft from a hepatitis C or B positive donor
  • previously received or is receiving an organ transplant other than a kidney
  • taking diltiazem, or any of the other disallowed medications during the 7 days prior to, and the 30 day trial period, or has been taking an investigational drug in the past 28 days
  • patient or donor known to be HIV positive

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The proportion of patients that achieve a tacrolimus whole blood trough concentration of >=10 ng/mL by Day 3 post-transplantation

Secondary Outcome Measures

Outcome Measure
Time to achieve first trough concentration of >=10 ng/mL. Comparative number of dose changes in each arm post-transplantation. Number of patients with whole blood trough concentration above the recommended therapeutic range (>15 ng/mL)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen-Cilag Pty Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (ACTUAL)

October 1, 2006

Study Completion (ACTUAL)

April 1, 2007

Study Registration Dates

First Submitted

February 24, 2006

First Submitted That Met QC Criteria

February 24, 2006

First Posted (ESTIMATE)

February 28, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

June 20, 2011

Last Update Submitted That Met QC Criteria

June 6, 2011

Last Verified

April 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR005020

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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