Clinical Centers for the HALT-Polycystic Kidney Disease Trials (U01)

描述（由申请人提供）：本次有限竞争的目的是继续患者随访并完成两项正在进行的HALTPolycystic Kidney Disease （PKD）临床试验。Tufts-NEMC和BIDMC的分包站点是HALT-PKD的七个患者入组站点中的两个。HALT-PKD试验由两项研究（A和B）组成，目前均处于患者入组阶段。HALT-PKD研究A正在评估肾血管紧张素-醛固酮系统（RAAS）阻断对548例肾小球滤过率（GFR）估计为60ml/min/1.73 m2的高血压PKD患者疾病进展的影响。在研究A中，使用2x2析因设计评估了研究药物对两种不同血压控制水平下结构进展的影响。据此，548名高血压ADPKD参与者被随机分配到四个研究组之一：1)ACE-I/ARB联合控制标准血压（收缩压120-130和舒张压70-80 mm Hg）；2) ACE-I单药治疗与标准血压控制；3) ACEI/ ARB联合治疗至低血压目标（收缩压95-110，舒张压60-75 mm Hg）；4) ACE-I治疗达到低血压目标。其他抗高血压药物根据需要加入以达到血压目标。该研究的主要终点是通过磁共振成像（MRI）测量肾脏总体积随时间变化的百分比。HALT-PKD研究B正在评估RAAS阻断对472例GFR 30- 60ml /min/1.73 m2的高血压PKD患者疾病进展的影响。研究B的主要终点是基线估计GFR、ESRD（开始透析或先发制人移植）或死亡减少50%的时间的复合终点。所有472例高血压ADPKD患者接受标准血压控制（收缩压110-130毫米汞柱，舒张压80毫米汞柱），并根据需要添加其他抗高血压药物。该申请将详细描述两个参与的临床中心，包括研究者和研究团队；遵守研究方案；研究程序的质量和安全；努力实现A研究对象137人、B研究对象118人的定向招生目标。

DESCRIPTION (provided by applicant): The purpose of this limited competition is to continue patient follow-up and complete the two ongoing HALTPolycystic Kidney Disease (PKD) clinical trials. Tufts-NEMC and the subcontracted site at BIDMC are two of seven patient enrolling sites for HALT-PKD. The HALT-PKD Trials are comprised of two studies (A & B) and are both currently in the patient enrollment phase. HALT-PKD Study A is evaluating the impact of reninangiotensin- aldosterone system (RAAS) blockade on progression of disease in 548 hypertensive PKD patients with estimated glomerular filtration rate (GFR) > 60ml/min/1.73 m2. In Study A, the effect of study medication on structural progression at two different levels of blood pressure control is assessed using a 2x2 factorial design. Accordingly, 548 hypertensive ADPKD participants are randomized to one of four study arms: 1) combination ACE-I/ARB with standard blood pressure (BP) control (systolic 120-130 and diastolic 70-80 mm Hg); 2) ACE-I monotherapy with standard BP control; 3) combination ACEI/ ARB treated to a low BP target (systolic 95-110 and diastolic 60-75 mm Hg); and 4) ACE-I treated to the low BP goal. Other antihypertensive agents are added as needed to meet the BP goals. The primary endpoint of the study is the percent change in total kidney volume, as measured by magnetic resonance imaging (MRI) over time. HALT-PKD Study B is evaluating the impact of RAAS blockade on progression of disease in 472 hypertensive PKD patients with estimated GFR 30-60 ml/min/1.73 m2. The primary endpoint of Study B is a composite endpoint of time to the 50% reduction of baseline estimated GFR, ESRD (initiation of dialysis or preemptive transplant), or death. All 472 hypertensive ADPKD participants are treated to a standard level of blood pressure control (systolic 110-130 mm Hg and diastolic 80 mm Hg), with addition of other antihypertensive agents as needed. This application will describe in detail the two participating clinical centers including the investigators and study teams; adherence to the study protocol; quality and safety of study procedures; and efforts being made to achieve the targeted recruitment goal of 137 study A and 118 study B subjects.