An Investigator-initiated, International, Multi-centre, Prospective, Randomized, Open-label, Parallel-group, Superiority, and Pragmatic Large Simple Trial (LST) to Determine Whether the Currently Recommended Strategy of Intensive Reduction of Serum Phosphate Concentration Towards the Normal Level Results in Significant Patient-centred Benefits in End-stage Kidney Disease (ESKD) Patients Receiving Dialysis.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 3,600
- 试验地点
- 116
- 主要终点
- Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event
研究概览
简要总结
During end-stage kidney disease, clinical guidelines suggest reducing elevated phosphate levels in the blood. However, the effect of lowering blood phosphate levels on important patient-centred outcomes has never been tested. This trial will evaluate whether compared to high levels, lowering blood phosphate levels would reduce death or major events due to heart disease, improve physical health, and be cost-effective.
详细描述
Hyperphosphataemia is highly prevalent in patients with end-stage kidney disease (ESKD) and associated with increased mortality risk. The Clinical Practice Guidelines suggest lowering elevated phosphate levels towards the normal range (level 2C suggestion). However, trial data demonstrating that treatments that lower serum phosphate will improve patient-centred outcomes are lacking.
The primary objective is to test the hypothesis that compared to a liberal serum phosphate concentration target of 2.0 to 2.5 mmol/L, intensive lowering of serum phosphate towards the normal level (≤1.50 mmol/L) with phosphate binders reduces the risk of fatal or non-fatal major cardiovascular events in ESKD patients receiving dialysis. The secondary objectives are to test the hypothesis that intensive lowering of serum phosphate towards the normal level with phosphate binders would improve physical health, fatigue, health-related quality of life, patient satisfaction, and pruritus; and be cost-effective.
In this pragmatic, multinational, randomised controlled large simple trial, a total of 3600 adult ESKD patients receiving dialysis will be randomised either to intensive (≤1.50 mmol/L) or liberalized (2.0-2.5 mmol/L) serum phosphate target. The choice and dose of phosphate binders will be at the treating physician's discretion and local practice to achieve and maintain serum phosphate concentration within the required target range according to randomisation. The primary endpoint is the composite endpoint of cardiovascular death, non-fatal major cardiovascular or peripheral arterial events. The secondary outcome measures will be individual components of the primary composite endpoint, all-cause death, and utility-based quality of life EQ5D-5L.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥45 years, or Age ≥18 years with diabetes,
- •ESKD on haemodialysis or peritoneal dialysis, for at least 3 months,
- •Currently prescribed at least one phosphate-lowering medication at any dose
- •Able to provide informed consent
排除标准
- •Elective kidney transplantation scheduled,
- •Concomitant major illness / comorbidity that may result in death in the next 6 months in the view of the treating physician,
- •Participation in an interventional study that is likely to affect serum phosphate concentration.
研究组 & 干预措施
Liberal phosphate target
Liberal serum phosphate target of 2.0 to 2.5 mmol/L.
干预措施: Liberal phosphate target (Drug)
Intensive phosphate target
Intensive serum phosphate target of ≤1.50 mmol/L.
干预措施: Intensive phosphate target (Drug)
结局指标
主要结局
Time to a composite endpoint of cardiovascular death or non-fatal major cardiovascular event
时间窗: 5 years
Time to a composite endpoint of cardiovascular death, non-fatal myocardial infarction or coronary revascularization, stroke, or peripheral arterial event.
次要结局
- Utility-based quality of life EQ5D-5L(5 years)
- Time to individual components of the primary composite endpoint,(5 years)
- Time to all-cause death(5 years)