Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Changes in left ventricular mass on cardiac MRI and arterial stiffness (assessed by pulse wave velocity).
研究概览
简要总结
Patients with kidney failure have a poor survival rate that is due to a much higher than average rate of heart and vascular disease. The reason that kidney failure causes heart disease is unknown but recent research suggests that a hormone called aldosterone, which is increased in patients with kidney disease may damage the heart and blood vessels.
The investigators propose, using a randomized blinded trial, to find out whether drugs that inhibit the actions of aldosterone have beneficial effects on the cardiovascular system in patients with kidney failure
详细描述
Cardiovascular disease leads to the death of over half of patients with chronic renal failure (CRF) but the causes of this 'vasculopathy' remain unknown. Aldosterone is present in the circulation of renal failure patients at high levels and is known to exert damaging effects upon the myocardium, vasculature and autonomic nervous system. Patients will be randomised to determine the effect of chronic treatment with an aldosterone receptor inhibitor on left ventricular mass, diastolic function, arterial stiffness and autonomic function. All of these endpoints are predictors of mortality so that the results of this study may yield information of prognostic value and provide the basis for a future mortality study.
Premature cardiovascular disease is the leading cause of mortality in CRF accounting for approximately 60% of deaths. Across the age range, cardiovascular mortality is 10 and 20 times greater than controls but in young patients the relative risk is extreme. Dialysis patients under the age of 45 have over 100 times the risk of cardiovascular death than the control population. An increased risk is also present in patients with mild renal impairment, which has been estimated to occur in approximately 8% of the population. Thus, renal dysfunction is a potentially important risk factor for coronary artery disease in the general population. This study builds upon previous and current BHF funded work by Dr Townend and colleagues in Birmingham (PG97/162 and PG02/153) which has resulted in a number of publications in the area of cardiovascular disease in renal failure but takes a new approach examining the potential role of aldosterone in renal 'vasculopathy'.
Pathophysiology of myocardial and vascular disease in chronic renal failure:
The main pathological features of the cardiovascular system of patients with renal failure are:
- LVH often accompanied by systolic and diastolic dysfunction.
- Arterial wall thickening, stiffening and calcification (arteriosclerosis).
- Coronary and peripheral artery atherosclerosis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Mild-moderate chronic kidney disease (glomerular filtration rate [GFR] 40-80 mls/min calculated by Cockroft-Gault equation)
- •Controlled blood pressure (< 130/80 mmHg)
- •On established (> 6 weeks) treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
排除标准
- •Diabetes mellitus
- •Clinical evidence of fluid overload or hypovolaemia
- •Recent (< 2 months) acute myocardial infarction
- •Left ventricular (LV) dysfunction (ejection fraction < 40% by echocardiography).
研究组 & 干预措施
Spironolactone
25mg spironolactone daily
干预措施: Spironolactone (Drug)
Placebo
matching placebo medication for the control group
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in left ventricular mass on cardiac MRI and arterial stiffness (assessed by pulse wave velocity).
时间窗: 9 months
次要结局
- Changes in aortic distensibility and large vessel augmentation(9 months)