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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
75
Tacrolimus, a calcineurin inhibitor, is the commonest immunosuppressive agent used for maintenance immunosuppression after solid organ transplantation. The mechanism of action involves binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the generation of nuclear factor of activated T-cells, a nuclear component, resulting in inhibition of transcription of lymphokines (interleukin-2, γ-interferon). The net result is the inhibition of T-lymphocyte activation.Tacrolimus is metabolized primarily by the CYP3A enzymes in the liver particularly the CYP3A5.
The Hospital for Sick Children
Toronto, Ontario, Canada
Time to Achieve Therapeutic Tacrolimus Drug Concentrations
The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations
Time frame: From Baseline to 30 days post-dose
Time to Maintain Stable Therapeutic Trough Concentrations
Defined as two consecutive concentrations at least 48 hours apart in the therapeutic range without any changes in tacrolimus dose
Time frame: From Baseline to 30 days post-dose
Clinical Adverse Events
The effect of pharmacogenetic dosing of tacrolimus for 48 hours on the frequency clinical adverse effects over 30±3 days.
Time frame: Over 30 days, +/- 3 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.