Limited Competition: Clinical Centers for the HALT-Polycystic Kidney Disease Tria

描述（由申请人提供）：常染色体显性多囊肾病（ADPKD）是最常见的遗传性肾病，也是该国肾衰竭的第三大常见原因。在ADPKD囊肿生长在肾脏随着时间的推移，由于囊肿的发展和扩大。早期ADPKD患者发生高血压，这与更快的肾衰竭进展速度相关。到目前为止，还没有开发出有效的治疗高血压和ADPKD患者，减缓疾病进展。肾素血管紧张素-醛固酮系统的激活与ADPKD高血压有关.现在有两类抗高血压药物抑制该系统的激活。这些包括血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻断剂（ARB）。目前尚不清楚这些药物联合使用是否能有效减缓ADPKD患者的肾衰竭进展，以及血压控制水平是否对减缓肾衰竭进展很重要。HALT是一项前瞻性纵向随机双盲研究，将在7家临床试验机构的1018例受试者中进行，为期4年。埃默里大学将研究254名受试者，涉及两个患者人群。研究A将涉及年龄17-45岁且肾功能正常（估计的GFR > 60 ml/min）的受试者，并且将确定通过磁共振成像（MRI）测量的肾大小的变化率。受试者还将被分为两个血压控制水平，<110/75（严格控制）或<130/80 mm Hg（标准控制）。在研究组B中，年龄18-64岁且肾功能低于正常（估计GFR 25-60 ml/min）的受试者将被治疗至相同水平的血压水平（<130/80 mm Hg）。研究B的复合主要终点包括至血清肌酐浓度加倍、肾脏替代治疗或死亡的时间。所有合格受试者将接受降压药物洗脱，接受基线评价，然后在研究期间进行剂量滴定期和维持期。本研究将确定双重抑制RAAS以及严格控制血压在预防ADPKD肾病进展中的疗效。

DESCRIPTION (provided by applicant): Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic renal disease and is the third most common cause of renal failure in this country. In ADPKD cysts grow in the kidneys over time due to cyst development and expansion. Early ADPKD patients develop hypertension which is associated with a faster rate of progression to renal failure. To date no effective therapy has been developed for patients with hypertension and ADPKD that slow progression of disease. Activation of the reninangeotensin- aldosterone system is associated with hypertension in ADPKD. There are now two classes of antihypertensive medications which inhibit the activation of this system. These include Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blocking Agents (ARB). It is not known whether combining these agents together will be effective in slowing progression of renal failure in ADPKD and if levels of blood pressure control are important in slowing progression of renal failure. HALT is a prospective longitudinal randomized double blinded study will be performed in 1018 subjects at 7 clinical sites over a period of four years. There will be 254 subjects studied at Emory University involving two patient populations. Study A will involve subjects' age 17-45 years with normal renal function (estimated GFR > 60 ml/min) and the rate of change in renal size measured by magnetic resonance imaging (MRI) will be determined. Subjects will also be separated into two levels of blood pressure control, <110/75 (rigorous control) or <130/80 mm Hg (standard control). In study Group B, subjects' age 18-64 years with less than normal renal function (estimated GFR 25-60 ml/min) will be treated to the same level of blood pressure level (<130/80 mm Hg). The composite primary end point for Study B includes time to doubling of serum creatinine concentration, renal replacement therapy or death. All eligible subjects will undergo washout from their antihypertensive medications, undergo a baseline evaluation, followed by a dose titration phase and a maintenance phase for the duration of the study. This study will determine the efficacy of dual inhibition of the RAAS as well as rigorous blood pressure control in preventing progression of renal disease in ADPKD.