Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation

Phase 2

Completed

• Conditions: Liver Transplantation; Heart Transplantation; Kidney Transplantation
• Interventions: Drug: Tacrolimus

• Registration Number: NCT01655563
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Tacrolimus is a standard and widely used maintenance immunosuppressive agent after solid organ transplantation.The purpose of this trial is to determine if dosing of tacrolimus through genetics will help in early attainment and maintenance of the correct dosage level in the early post-transplant period. This pilot dose-finding trial will help to determine a dosing strategy guided by genotypes and age for solid organ transplant recipients that will be further validated through a multi-centre trial as an immediate next step. The study hypothesizes that dosage levels determined through age and genotype will be attained faster and more accurately than the standard dosing procedures in the 14-days after the transplant. Further, this study hypothesizes that a genotype and age dosing strategy will cause a faster recovery (tested through the kidneys' ability to clear creatine from the blood) and result in lower frequencies of adverse effects and rejection of the transplant.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-07-27
• Study First Submitted QC: 2012-08-01
• Study First Posted: 2012-08-02
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Results First Submitted: 2018-10-01
• Results First Submitted QC: 2019-07-12
• Results First Posted: 2019-08-28
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-27
• Last Update Posted: 2019-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Age < 18 years old
• Assessed and/or listed for heart, kidney, liver transplantation
• Planned oral or enteral maintenance immunosuppression with tacrolimus post transplant
• Informed consent of legal guardian

Exclusion Criteria

• Contra-indications to oral or enteral tacrolimus
• Co-morbidities that preclude standard dosing e.g. significant renal or hepatic insufficiency
• Participation in other investigational drug trials within 30 days of study initiation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Dosing Arm	Tacrolimus	Patients in the standard arm will receive standard starting dose of tacrolimus that is clinically used i.e. 0.1 mg/kg/dose twice a day.
Pharmacogenetic Arm	Tacrolimus	Patients in the pharmacogenetic arm will receive a starting dose that is assigned based on age and CYP3A5 expressor status. Patients that are CYP3A5 expressors will receive the higher end of the dose range compared to non-expressors. All doses recommended represent clinically acceptable and safe dose ranges used at our institution. CYP3A5 non-expressor starting dose: Greater than 6 years of age - 0.075 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.1 mg/kg/dose q12 hours CYP3A5 expressor starting dose: Greater than 6 years of age - 0.15 mg/kg/dose q12 hours; Less than or equal to 6 years of age - 0.2 mg/kg/dose q12 hours

Primary Outcome Measures

Name	Time	Method
Time to Maintain Stable Therapeutic Trough Concentrations	From Baseline to 30 days post-dose	Defined as two consecutive concentrations at least 48 hours apart in the therapeutic range without any changes in tacrolimus dose
Time to Achieve Therapeutic Tacrolimus Drug Concentrations	From Baseline to 30 days post-dose	The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations

Secondary Outcome Measures

Name	Time	Method
Clinical Adverse Events	Over 30 days, +/- 3 days	The effect of pharmacogenetic dosing of tacrolimus for 48 hours on the frequency clinical adverse effects over 30±3 days.

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada