Tacrolimus Associated Tremors in Liver Transplant Recipients: a Randomized Open Label Trial Comparing De Novo Extended-release Once Daily (LCP-TAC) and Twice Daily Immediate-release (IR-TAC) Tacrolimus Formulations
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Proportion of patients with tacrolimus induced tremors or worsening tremors or tacrolimus discontinuation due to neurotoxicity at 8 weeks post transplantation
研究概览
简要总结
This is a randomized open label study in de novo liver transplant recipients that aims to compare the risk of tacrolimus induced tremors with once daily extended-release formulation, Envarsus, versus the twice daily immediate-release formulation. Both formulations of tacrolimus are currently approved for the prevention of rejection in liver transplant patients.
详细描述
Purpose: This study is designed to evaluate the incidence and severity of tremors with two different tacrolimus formulations (LCPT versus IR-TAC) when administered in combination with mycophenolate and short term corticosteroids in de novo liver transplant (LT) recipients.
Hypothesis
In de novo liver transplant recipients, an LCPT-based immunosuppression regimen, in combination with mycophenolate and short term steroids offers improved neurotoxicity profile as evidenced by lower incidence and severity of tremors and treatment discontinuation when compared to an identical regimen using twice-daily immediate-release tacrolimus.
Rationale: Tacrolimus is the first line immunosuppressive agent in all organ transplantation and its use is associated with improved patient and graft outcomes. Neurotoxicity including headaches and tremors are amongst common dose limiting toxicities associated with tacrolimus early after liver transplantation. Mitigation strategies include dosage reduction or switch to CSA, both of which can put patient at risk of rejection and other toxicities. LCPT is a new extended release formulation with improved PK parameters and evidence of improved tolerability (lower risk of tremors) in renal transplant population. In this study, we will compare the incidence and severity of tremors associated with IR-TAC, which is currently standard of care at our institution, with LCPT, which is a new dosage form added to the hospital formulary. We will be using wearable sensors to assess the severity of tremors. Furthermore, the objective and systematic documentation of tremor severity during the first 8 weeks after transplantation will provide granular data that will elucidate the natural history of tacrolimus induced tremors early post liver transplantation.
Research design: This is a single centre, prospective, randomized, open label, parallel group trial in adult de novo liver transplant recipients. Patients will be randomized (1:1) to either LCPT or IR-TAC, both groups will receive mycophenolate and short term steroids according to the standard of care protocol. This is a superiority study.
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
- •Adults aged 18 years or older
- •Recipients of a first-time liver transplant
- •eGFR more than 30 ml/min on the day of tacrolimus initiation
- •All patients who are eligible to initiate Tacrolimus within 7 days post-liver transplant
- •Informed consent
排除标准
- •Recipients of prior organ transplant
- •Need for hemodialysis either prior or following liver transplantation
- •Recipients of living donor liver or split deceased donor liver allografts
- •Recipients of combined liver/kidney transplants
- •Recipients receiving liver allografts from donors with HCV viremia (detected through nucleic acid testing or other means)
- •Patients with a history of tremor prior to transplantation including essential tremors, Parkinson's or Parkinsonian syndromes
- •Patients receiving concomitant medications known to induce tremors such as dopamine blocking agents
- •Baseline TSH, T3, T4 indicating hyperthyroidism
研究组 & 干预措施
LCPT
干预措施: Tacrolimus Extended Release Oral Tablet (Drug)
IR-TAC
干预措施: Tacrolimus, Immediate Release, Oral (Drug)
结局指标
主要结局
Proportion of patients with tacrolimus induced tremors or worsening tremors or tacrolimus discontinuation due to neurotoxicity at 8 weeks post transplantation
时间窗: 8 weeks post transplantation
Composite end point of proportion of patients with new tremor as defined by Kinesia One average score of 1 or greater or an increase from baseline of greater than or equal to 1 point at week 8 after transplantation, or tacrolimus discontinuation due to neurotoxicity (tremor, headaches, seizure or dysarthria).
次要结局
- Proportion of patients reaching the composite end point of death, graft loss or biopsy proven acute cellular rejection (BPAR) at 12 months post transplantation(12 months post transplantation)
- Tremor related quality of life satisfaction as assessed by the Quality of Life in Essential Tremor (QUEST) scale(8 weeks post transplantation)
- Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 8 weeks after transplant(8 weeks post transplant)
- Immunosuppression medication adherence as assessed by the Simplified Medication Adherence Questionnaire (SMAQ) at 12 months after transplant(12 months post transplantation)
研究者
Trana Hussaini
Clinical Assistant Professor
University of British Columbia