Arterial Stiffness and Arterial Calcifications Evolution in ESRD Haemodialysis Patients Treated by Sevelamer or Calcium Acetate
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- changes in arterial stiffness parameters
研究概览
简要总结
End-stage renal disease (ESRD) is a state of increased arterial stiffness of extensive vessel calcifications, compared with the non-renal population. Both arterial stiffness and arterial calcifications are potent predictors of all-cause and cardiovascular mortality in ESRD patients. Several studies have documented the direct relationship between the extent and severity of arterial/coronary calcifications and outcome in dialysis patients. The relationship is strong no matter if arterial calcifications were quantified by electron-beam computed tomography or a radiological calcification score. Calcifications are early and progressive events in these patients. PWV is strongly related to the degree of sonographic determined arterial calcifications and EBCT-derived coronary artery calcium score in chronic kidney disease patients.
Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled.
According to recent studies, sevelamer hydrochloride is a potent non-calcium-containing phosphate binder, well tolerated in ESRD. Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients. Moreover, sevelamer has a favorable effect on the lipid profile.
Less is known about the relationship between sevelamer treatment and progression of arterial stiffness. To date, there is one single study examining the influence of sevelamer (versus calcium carbonate) on the evolution of arterial stiffness in a very small number (N=15) of haemodialysis patients. These study used the same patients as historical controls, thus being methodologically rather weak. Moreover, the follow-up was quite short - 6 month.
The aim of the trial is to to quantify, in a randomized opened-labeled controlled trial the effect of sevelamer hydrochloride on the evolution of arterial stiffness parameters (pulse wave velocity and the augmentation index) in chronic haemodialysis patients and to correlate these parameters with arterial calcification assessed by a previous described radiological score of arterial calcification and echocardiographic parameters (left ventricular hypertrophy, LV dilatation, systolic and diastolic dysfunction).
详细描述
End-stage renal disease (ESRD) is a state of increased arterial stiffness of extensive vessel calcifications, compared with the non-renal population. Both arterial stiffness and arterial calcifications are potent predictors of all-cause and cardiovascular mortality in ESRD patients. Underlying mechanisms for increased stiffness in uremia are not well-defined, but may include: chronic fluid overload, arterial calcifications, microinflammation, increased sympathetic hyperactivity, activation of the renin-angiotensin system, increased lipid oxidation, and abnormalities of the nitric oxide system.
Several studies have documented the direct relationship between the extent and severity of arterial/coronary calcifications and outcome in dialysis patients. The relationship is strong no matter if arterial calcifications were quantified by electron-beam computed tomography or a radiological calcification score. Calcifications are early and progressive events in these patients. PWV is strongly related to the degree of sonographic determined arterial calcifications and EBCT-derived coronary artery calcium score in chronic kidney disease patients.
Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled.
Sevelamer hydrochloride is a potent non-calcium-containing phosphate binder, well tolerated in ESRD. Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients. Moreover, sevelamer has a favorable effect on the lipid profile.
Less is known about the relationship between sevelamer treatment and progression of arterial stiffness. To date, there is one single study examining the influence of sevelamer (versus calcium carbonate) on the evolution of arterial stiffness in 15 HD patients. These study used the same patients as historical controls, thus being methodologically rather weak. Moreover, the follow-up was quite short - 6 month.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •more than 3 months on haemodialysis
- •willingness to participate
- •age 18-60 yrs
- •pre-dialysis blood pressure 120-160 mmHg in the last month prior to the initiation of study or recent (<1 Mo) addition of a new antihypertensive drug
- •iPTH at entry 200-800 pg/mL (as per severe hyperparathyroidism)
- •serum calcium at entry 2.2-2.6 mmol/L
排除标准
- •haemodynamic instability
- •uncontrolled hypertension
- •any severe, debilitating disease associated with a reduced survival
- •any major cardiovascular event in the last 12 month before study
- •cinacalcet therapy before study entrance
- •history of parathyroidectomy
- •documented history of poor compliance
- •serious gastrointestinal disease
研究组 & 干预措施
I
Calcium acetate 670 mg tablets
干预措施: Calcium acetate (Drug)
II
label sevelamer (RenagelR) 800 mg tablets
干预措施: Calcium acetate (Drug)
II
label sevelamer (RenagelR) 800 mg tablets
干预措施: Sevelamer (Drug)
结局指标
主要结局
changes in arterial stiffness parameters
时间窗: 6 months
changes in calcification score
时间窗: 6 months
次要结局
- composite of all-cause mortality, cardiovascular mortality and major cardiovascular events(1 year)
研究者
Liliana Garneata
MD. PHD
Romanian Society of Nephrology