Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation

The Hospital for Sick Children

Status and phase: Completed; Phase 2

Conditions: Liver Transplantation; Kidney Transplantation; Heart Transplantation

Treatments: Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT01655563

1000026524

Details and patient eligibility

About

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.

Enrollment: 75 patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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75 participants in 2 patient groups

Standard Dosing Arm

Active Comparator group

Description:

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.

Treatment:

Drug: Tacrolimus

Pharmacogenetic Arm

Experimental group

Description:

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

Treatment:

Drug: Tacrolimus