The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Change in Cr EDTA clearance
研究概览
简要总结
The purpose of this study is to assess whether the diuretic drug spironolactone can prevent chronic damage to transplanted kidneys caused by the medication that prevents rejection.
Spironolactone prevents the effects of the hormone aldosterone. Aldosterone is suspected of being involved in the processes leading to chronic rejection of transplanted kidneys. Hence, by blocking the effects of aldosterone we hope to be able to prevent loss of kidney function in transplant patients.
详细描述
AIM: The purpose of this study is to assess whether spironolactone can prevent the formation of fibrosis in transplanted kidneys.
BACKGROUND: Calcineurin inhibitors (CNI) are one of the cornerstones of immunosuppressive therapy after kidney transplantation. The introduction of CNI has caused a significant decrease in acute rejections. However, CNI also have known side effects. These include the formation of tubulointerstitial fibrosis in the transplanted kidney, contributing over time to impaired kidney function and reduced graft survival.
The mineralocorticoid aldosterone may be involved in the development of renal fibrosis. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CNI nephrotoxicity and that the mineralocorticoid-receptor-blocker spironolactone could be a useful agent to prevent it.
METHODS: This study is a randomized, placebo-controlled, double-blind study in which 170 renal transplant patients will be recruited from two nephrological departments in Southern Denmark. Patients will be randomized to three years of treatment with either spironolactone or placebo added to the standard immunosuppressive treatment. Renal graft biopsies, various molecular tests of tissue, blood and urine, chrome-EDTA clearance, 24-hour bloodpressure measurement and blood samples will be performed at inclusion, after 1 year, 2 years and upon completion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age > 18 years
- •Proteinuria < 3 g/24 hours
- •Creatinine clearance ≥ 30 mL/min
- •S-Potassium < 5,5 mmol/L
- •Negative pregnancy test at the inclusion and anticonception
排除标准
- •Intolerance to spironolactone
- •Creatinine clearance < 30 ml/min
- •S-Potassium ≥ 5,5 mmol/L
- •Resin or digoxine treatment
- •Pregnancy or planned pregnancy
- •Relevant organic, systemic or mental illness
- •Anticipation of lack of compliance or understanding the study
研究组 & 干预措施
Spironolactone
干预措施: Spironolactone (Drug)
Placebo
干预措施: placebo (Drug)
结局指标
主要结局
Change in Cr EDTA clearance
时间窗: 0, 1 year, 2 years, 3 years
次要结局
- Reduced blood pressure (change from baseline)(0, 1 year, 2 years, 3 years)
- Reduced urine protein levels (change from baseline)(0, 1 year, 2 years, 3 years)
- Reduced fibrosis (change from baseline)(0, 2 years)
- Cardiovascular events(3 years)
研究者
Line Aas Mortensen
Principal Investigator
Odense University Hospital