Conversion From Tacrolimus to Envarsus in Rapid Metabolizers Post Kidney Transplant Protects Against BK Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- Number of Participants With Viruria >500 Copies
研究概览
简要总结
The purpose of this study is to assess if the use of Envarsus in place of Tacrolimus-immediate release (IR) in rapid metabolizers post kidney transplant will reduce incidence of BK infection. Efficacy evaluations will include measurement of urine and serum BK values at specified time points and review of any biopsy for BK virus nephropathy. Incidence of rejection, graft failure, and graft dysfunction will also be measured at specified time points.
详细描述
This will be a single center prospective case control study. The investigators expect 40% of patients will develop BK viruria, 20% BK viremia, 5% BK viral nephropathy (BKVN). Patients will be managed using standard of care for the investigator's center (thymoglobulin induction, tacrolimus/mycophenolate/prednisone). Target tacrolimus level is 8-12 ng/mL for the first 6 months post transplant and 6-9 ng/mL thereafter. BK urine/serum is monitored at 1, 3, 6, 9, 2 months post transplant. A population of 100 patients is calculated to show significant difference for p value < 0.05.
Population:
Study Group: Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at post-transplant month 1, who have a tacrolimus concentration/dose of < 1 and a steady state therapeutic level will be eligible. Patients who consent will be converted to Envarsus at 20% reduction in tacrolimus dose.
Control Group: Post transplant patients (kidney transplant alone performed between 10-2016 and time of enrollment) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at post-transplant month 1 and tacrolimus concentration/dose of < 1 at post-transplant month 1, and BK data available for months 2, 3, 6, 9,12 post transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years of age at the time of study entry
- •Recipient of a deceased or living donor kidney transplantation
- •Maintenance immunosuppression consisting of tacrolimus/ mycophenolate mofetil (MMF)/mycophenolic acid (MPA) (≥1000 mg/720 mg daily) ± prednisone (≤10 mg/day)
- •Patient is less than or at 8 weeks post transplant with a negative serum BK Virus screen at 3-4 weeks post transplant
- •Patient has a tacrolimus drug dose/concentration of > 1 with therapeutic tacrolimus levels.
- •Women of childbearing potential defined as all women physiologically capable of becoming pregnant, must have reviewed Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) and have a negative pregnancy test upon study entry.
- •Female (and male) subjects with reproductive potential must agree to use a highly effective method of birth control for the duration of the study. Please note that according to the US product information for MMF/MPA, two reliable forms of contraception must be used simultaneously unless female sterilization, male sterilization, post-menopausal status or total abstinence is the chosen method.
排除标准
- •Inability or unwillingness of a patient to give written informed consent or comply with study protocol
- •History of graft loss from acute rejection within 1 year after any previous kidney transplant
- •History of previous liver, heart, pancreas, or lung transplant
- •History of cellular rejection of current allograft prior to enrollment.
- •Serum BK virus ≥500 copies/ml by polymerase chain reaction (PCR) at the time of study entry
- •Female subjects who are pregnant or breast feeding
- •Participation in any other studies with investigational drugs or regimens in the preceding year from the time of study entry
- •Any condition or prior treatment which, in the opinion of the investigator, precludes study participation
- •Patients requiring the use of azathioprine or a class of drugs that inhibit the mammalian target of rapamycin (mTOR inhibitors)
- •Patients with active peptic ulcer disease
研究组 & 干预措施
Study Group
Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at month 1, whom have a concentration/dose of < 1 and a steady state therapeutic level will be eligible. Patients will be converted to envarsus at 20% reduction in dose.
干预措施: Study Group (Drug)
Control Group
Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of < 1 at month 1, and BK data available and month 2,3, 6,9,12.
干预措施: Control Group (Drug)
结局指标
主要结局
Number of Participants With Viruria >500 Copies
时间窗: at 300 days
Participants will experience less BK infection episodes based on viruria reported with \>500 copies.
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.
时间窗: From baseline to 210 days
The evidence of BK virus infection will be measured by viruria \>500 copies.
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.
时间窗: at 300 days
The evidence of BK virus infection will be measured by viremia \>500 copies.
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.
时间窗: at 300 days
The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.
时间窗: at 300 days
Safety will be assessed for all Grade 3 or higher infection
次要结局
- Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.(at 300 days)
研究者
Graham C. Towns
Principal Investigator
University of Alabama at Birmingham