A Pharmacogenetic Trial of Tacrolimus Dosing After Pediatric Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Time to Maintain Stable Therapeutic Trough Concentrations
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Standard Dosing Arm
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.
干预措施: Tacrolimus (Drug)
Pharmacogenetic Arm
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
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Time to Maintain Stable Therapeutic Trough Concentrations
时间窗: 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
时间窗: From Baseline to 30 days post-dose
The primary outcome (efficacy) was time to achieve therapeutic tacrolimus trough concentrations
次要结局
- Clinical Adverse Events(Over 30 days, +/- 3 days)
研究者
Seema Mital
Staff Cardiologist
The Hospital for Sick Children