Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation

Kidney Transplantation Clinical Trial

Official title:

A Pharmacogenetic Trial of Tacrolimus Dosing After Pediatric Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01655563
• Other study ID #: 1000026524
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: February 2016

Study information

• Verified date: November 2019
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Transplantation
• Kidney Transplantation
• Liver Transplantation

Intervention

Drug:
• Tacrolimus
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, ?-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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Min S, Papaz T, Lafreniere-Roula M, Nalli N, Grasemann H, Schwartz SM, Kamath BM, Ng V, Parekh RS, Manlhiot C, Mital S. A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation. Pediatr Transplan — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Achieve Therapeutic Tacrolimus Drug Concentrations	The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations	From Baseline to 30 days post-dose
Primary	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	From Baseline to 30 days post-dose
Secondary	Clinical Adverse Events	The effect of pharmacogenetic dosing of tacrolimus for 48 hours on the frequency clinical adverse effects over 30±3 days.	Over 30 days, +/- 3 days