Assessment of Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From Immediate Release Tacrolimus to Extended Release Tacrolimus.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Urinary neutrophil gelatinase-associated lipocalin (NGAL)
研究概览
简要总结
Immediate release (IR) tacrolimus peaks in the first two hours after administration. These peak levels are influenced by CYP3A5 expression with expressors requiring higher total daily doses with higher peak levels compared to non-expressors. Tacrolimus XR (Envarsus) is a once daily formulation with delayed absorption and lower peak levels while maintaining similar trough levels as seen with IR tacrolimus. A randomized trial of conversion from IR tacrolimus to tacrolimus XR in kidney transplant recipients have shown similar efficacy and adverse events between the two groups but no improvement in estimated GFR. However, urinary biomarkers of acute kidney injury associated with changes in tacrolimus dosing may be more sensitive then serum creatinine. The objective of this study is to assess renal tubular injury in heart transplant recipients who are converted from immediate release to tacrolimus XR. The hypothesis is that the delayed absorption and lower peak levels of tacrolimus XR will lead to less tubular injury and improved renal function without increased risk to the heart allograft.
详细描述
The primary outcome is change in urinary NGAL expression with conversion from IR tacrolimus to tacrolimus XR. In aim 1, changes in urinary biomarkers of tubular injury at 4 weeks after conversion to tacrolimus XR with stable trough levels will be assessed. These changes will be assessed by CYP3A5 expressor category that will be determined by genotyping of a single gene for variants. The changes in GFR using the creatinine-cystatin C CKD-EPI equation will be assessed. In aim 2, the rate of rejection as defined as treated rejection within the last 30 days for any grade > 1R or AMR or acute graft dysfunction (LV ejection fraction drop > 10%) will be looked. The cardiac allograft vasculopathy based on coronary angiography +/- IVUS and right heart catheterization hemodynamics at baseline and 1 year post conversion will also be evaluated. In addition to changes in cardiac function, the changes in blood pressure, serum glucose, and cholesterol in the first year after conversion will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stable, heart-only transplant recipient within 10 years of transplantation
- •18 -80 years old
- •Currently taking IR Tacrolimus
- •Baseline eGFR> 30mL/min/1.73m2
排除标准
- •Multiple organ transplant recipients
- •Less than 18 years old
- •Greater than 80 years old
- •Heart-only transplants recipients with active malignancy, rejection, or greater than 10 years from transplantation
研究组 & 干预措施
Extended Release Tacrolimus
All participants who consent to the study will be in this group.
干预措施: Conversion from IR Tacrolimus to XR Tacrolimus (Drug)
结局指标
主要结局
Urinary neutrophil gelatinase-associated lipocalin (NGAL)
时间窗: 4 weeks
Change in Urinary NGAL level (ng/mL)
次要结局
- Estimated Glomerular Filtration Rate (eGFR)(4 weeks)
- Microalbuminuria(4 weeks)
- CYP3A5 expressor category(Baseline)
- Serum glucose(1 year)
- LDL Cholesterol(1 year)
- Heart transplant rejection(1 year)
- Cardiac allograft vasculopathy(1 year)
- Blood pressure(1 year)
研究者
Sanjeev Akkina
MD, Associate Professor of Medicine
Loyola University