Feasibility, Efficacy And Safety Of De Novo Extended-Release Tacrolimus Following Liver Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 2
- 主要终点
- Safety of Envarsus as indicated by adverse events
研究概览
简要总结
Medications used after transplant to prevent rejection are associated with many side effects. Tacrolimus side effects include kidney dysfunction; tremor, headaches, difficulty sleeping, change in sensation (legs), seizure, or confusion; high blood pressure; anemia, or low blood cell counts; diabetes; abnormal cholesterol and weight gain. The investigators want to use a new, approved, formulation of the standard medication (Envarsus) as they believe it may be associated with reduced side effects. The investigators would like to assess how safe it is to use this medication and how well it works in comparison to currently used formulations. The investigators will study if there are less side effects and will study clinical outcomes (including how well the liver does and if there is need for hospitalizations after transplant).
The investigators hope that this information will improve the care provided to and outcomes in patients following liver transplant.
详细描述
PURPOSE
To assess the impact of Envarsus on toxicity and clinical outcomes in participants following liver transplant. Tacrolimus-based immunosuppression is the standard of care following liver transplantation (LT). This medication is associated with significant toxicity including renal dysfunction, increased risk of diabetes and neurotoxicity. Of note, both nephrotoxicity and neurotoxicity occur at elevated peak serum tacrolimus blood concentrations and improve when the dose is reduced or discontinued. Envarsus does not have the high peak seen with initial dosing in the other formulations. This may be one of the reasons Envarsus use improves tremor associated with tacrolimus use.
HYPOTHESES
Use of extended-release tacrolimus following LT will be: 1. Effective and safe. 2. Without any difference in rejection. 3. Less nephrotoxic with reduced incidence of renal impairment. 4. Better with regard to features of metabolic syndrome including myosteatosis. 5. Less neurotoxic. 6. Better with regard to both graft and patient survival when compared to immediate-release tacrolimus (Prograf®).
JUSTIFICATION
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Adult individuals transplanted at the University of Alberta
排除标准
- •Individuals with congenital long QT syndrome
- •Patients with elevated bilirubin > 100 umol/L post-LT (at day 3)
- •Patients with chronic kidney disease (eGFR < 45 ml per minute per 1.73 m2)
- •Patients with acute kidney injury requiring discontinuation of calcineurin inhibitors.
- •Patients who have hepatocellular carcinoma, require a re-transplant, or receive multi-visceral transplant
研究组 & 干预措施
Prograf (SOC)
Prograf tablet Dose 0.10 - 0.15mg/Kg daily Frequency: 2 doses per day (dose above split in half for each dose)
干预措施: Prograf (SOC) (Drug)
Envarsus
Envarsus tablet Dose 0.11 - 0.13 mg/Kg/day Frequency: once per day
干预措施: Envarsus Oral Product (Drug)
结局指标
主要结局
Safety of Envarsus as indicated by adverse events
时间窗: 1 year
Adverse events include frequency of transplant rejection, and changes from baseline in clinical laboratory parameters
次要结局
- Number of patients with metabolic syndromes [diabetes](1-10 years)
- Patient Survival(1-10 years)
- Graft Survival(1-10 years)
- Muscularity assessment(1 year)
- Impact on quality of life (QOL) - EuroQuol Visual Analogue Scale (VAS)(1 year)
- Incidence of renal impairment(1-10 years)
- Incidence of neurotoxicity(1 years)
- Length of stay in hospitalized patients(1-10 years)
- Incidence of Intensive Care Unit (ICU) admission(1-10 years)
- Length of Intensive Care Unit admission(1-10 years)
- Incidence of hospitalizations(1-10 years)
- Impact on quality of life (QOL) - Chronic Liver Disease Questionnaire(1 year)
- Impact on quality of life (QOL) - EuroQuol-5Dimensions-5 Levels Questionnaire(1 year)