Clinical Trial to Slow the Progression of ADPKD

减缓 ADPKD 进展的临床试验

• 批准号: 7920516
• 负责人: ROBERT W SCHRIER
• 金额: $ 30.08万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920516
• 关键词: Adverse effects; Age; Albuminuria; Aldosterone; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Arrhythmia; Autosomal Dominant Polycystic Kidney; Blood Pressure; Cardiovascular system; Cessation of life; Clinical; Clinical Trials; Combined Modality Therapy; Cyst; Cystic kidney; Disease; End stage renal failure; Excretory function; Fibrosis; Filtration; Frequencies; Goals; Growth Factor; Heart; Heart Diseases; Heart failure; Hospitalization; Hypertension; Hypotension; Individual; Injury; Kidney; Kidney Failure; Left Ventricular Mass; Magnetic Resonance Imaging; Measures; Medical; Myocardial Infarction; Oxidants; Pain; Patients; Pharmaceutical Preparations; Placebos; Principal Investigator; Quality of life; Questionnaires; Randomized; Renal Blood Flow; Renal function; Renin-Angiotensin-Aldosterone System; Symptoms; Time; base; blood pressure regulation; design; prevent; prospective; urinary

DESCRIPTION (provided by applicant): The HALT-PKD study is the first prospective clinical interventional study for autosomal dominant polycystic disease (ADPKD). The goal of the HALT PKD study is to slow or prevent the progression of the kidney and heart disease in patients with early (Study A) or later (Study B) ADPKD. The focus of the HALT-PKD study is to block the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney and heart. Because of the local effects of the cysts on the kidney, the circulating and intrarenal RAAS is stimulated in ADPKD patients. The activation of the RAAS results in several consequences which have the potential to increase progression of kidney and heart complications in ADPKD. These include (1) raising blood pressure, (2) increasing kidney and heart fibrosis, (3) increasing oxidant injury of kidney and heart, (4) increasing growth factors which can stimulate increase proliferation of kidney cysts, and (5) increase remodeling of heart which predisposes to heart failure, heart attacks, and heart arrhythmias. There are substantial results demonstrating early hypertension and activation of the RAAS in subjects with ADPKD. Subjects with ADPKD will be separated into two groups based on renal function and age. Group A (Glomular Filtration Rate or GFR > 60 ml/min/1.73 m2, ages 15 to 49 years) and Group B (GFR 30-60 ml/min/1.73 m2, ages 18 to 64 years). Group A subjects will be randomized in a 2-by-2 design to treatment with an Angiotensin Converting Enzyme Inhibitor (ACE-1) and an Angiotensin Receptor Blocker (ARB) versus an ACE-I plus placebo medication and to Standard (< 130/80 mm Hg) or Rigorous (< 110/75 mm Hg) blood pressure control. Study A primary endpoint is the percent change in total kidney size as measured by Magnetic Resonance Imaging (MRI). Study B subjects will be randomized to treatment with a combination of ACE-I/ARB therapy or ACE-I therapy alone, with both groups treated to Standard levels of blood pressure control (< 130/80 mm Hg). The primary endpoint for Study B is a composite endpoint of time to the 50% reduction of baseline eGFR, eGFR <20 ml/min/1.73 m2, end stage renal disease (ESRD) or death.

描述（由申请人提供）：HALT-PKD研究是常染色体显性多囊病（ADPKD）的第一项前瞻性临床介入研究。 HALT PKD研究的目的是减慢或防止早期（研究A）患者（研究A）患者（研究B）ADPKD的肾脏和心脏病的进展。 HALT-PKD研究的重点是阻止肾素 - 血管紧张素 - 醛固酮系统（RAAS）对肾脏和心脏的影响。由于囊肿对肾脏的局部作用，因此在ADPKD患者中刺激了循环和肾内RAA。 RAAS的激活导致几种后果，有可能增加ADPKD中肾脏和心脏并发症的进展。其中包括（1）升高血压，（2）增加肾脏和心脏纤维化，（3）增加肾脏和心脏的氧化剂损伤，（4）增加生长因子可以刺激增加肾脏囊肿的增殖，以及（5）增加重塑心脏易感性，心脏病发作和心律不齐的心脏。有实质性的结果，证明了ADPKD受试者中RAA的早期高血压和激活。具有ADPKD的受试者将根据肾功能和年龄分为两组。 A组（肾小球过滤率或GFR> 60 mL/min/1.73 m2，年龄15至49岁）和B组（GFR 30-60 ml/min/min/1.73 m2，年龄18至64岁）。 A组受试者将在2 by-2设计中随机分组，以使用血管紧张素转化酶抑制剂（ACE-1）和血管紧张素受体阻滞剂（ARB）进行治疗，而ACE-I Plus安慰剂药物和标准药物（<130// 80 mm Hg）或严格（<110/75 mm Hg）血压控制。研究主要终点是通过磁共振成像（MRI）测量的总肾脏大小的百分比变化。研究B受试者将通过ACE-I/ARB治疗或ACE-I治疗的组合随机分配治疗，两组都接受了标准水平的血压控制水平（<130/80 mm Hg）。研究B的主要终点是降低基线EGFR 50％的综合时间终点，EGFR <20 mL/min/1.73 m2，终阶段肾脏疾病（ESRD）或死亡。