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

描述(由申请者提供)：本次有限竞赛的目的是继续患者随访，并完成正在进行的两项HALT多囊肾病(PKD)临床试验。塔夫茨-NEMC和BIDMC的分包站点是HALT-PKD七个患者登记站点中的两个。HALT-PKD试验由两项研究(A和B)组成，目前都处于患者登记阶段。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名高血压PKD患者疾病进展的影响，估计肾小球滤过率(GFR)和GT；60ml/min/1.73m2。在研究A中，研究药物在两种不同血压控制水平下对结构进展的影响采用2x2析因设计进行评估。因此，548名高血压ADPKD参与者被随机分成四组：1)将ACE-I/ARB与标准血压控制(收缩压120-130和舒张压70-80 mm Hg)相结合；2)单一使用ACE-I治疗与标准血压控制；3)将ACEI/ARB联合治疗为低血压目标(收缩压95-110，舒张压60-75 mm Hg)；以及4)将ACE-I治疗为低血压目标。根据需要添加其他降压药，以达到BP的目标。研究的主要终点是通过磁共振成像(MRI)测量的总肾脏体积随时间的变化百分比。HALT-PKD研究B正在评估RAAS阻断对472名高血压PKD患者病情进展的影响，这些患者的GFR估计为30-60毫升/分钟/1.73平方米。研究B的主要终点是基线估计GFR减少50%、ESRD(开始透析或预防性移植)或死亡的综合终点。所有472名高血压ADPKD患者均接受标准水平的血压控制(收缩压110-130毫米汞柱，舒张压80毫米汞)治疗，并根据需要添加其他降压药。本申请将详细介绍两个参与研究的临床中心，包括研究人员和研究团队；对研究方案的遵守；研究程序的质量和安全；以及为实现137个研究A和118个研究B受试者的定向招募目标所做的努力。

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.