Tacrolimus vs Intensive Prednisone in Pediatric FSGS

他克莫司与强的松在儿科 FSGS 中的比较

• 批准号: 6802287
• 负责人: Frederick Kaskel
• 金额: $ 22.99万
• 依托单位: MONTEFIORE MEDICAL CENTER (BRONX, NY)
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802287
• 关键词: FK506; adolescence (12-20); atorvastatin; clinical research; clinical trials; cooperative study; glomerular filtration rate; glomerulosclerosis; histopathology; human subject; human therapy evaluation; hyperlipidemia; hypertension; kidney disorder chemotherapy; losartan; middle childhood (6-11); outcomes research; patient oriented research; prednisone; preschool child (1-5); proteinuria

DESCRIPTION (provided by applicant): Focal Segmental Glomerulosclerosis (FSGS) is a major cause of chronic kidney disease in childhood. This glomerulopaty is more frequent in minority populations, and often recurs in the transplanted kidney. Despite advances particulary in molecular genetics, the cause and optimal treatment of this condition remains poorly defined. Uncontrolled studies in adults with FSGS support the use of prolonged prednisone therapy. Preliminary data in children suggests that the calcineurin inhibitor tacrolimus may be efficacious in patients who have been refractory to other therapies. The purpose of this multicenter study is to compare the relative efficacy of tacrolimus with that of intensive prednisone therapy in preventing the progression of primary FSGS. This represents the first controlled evaluation of these two promising therapies in children with FSGS. We are proposing a randomized, open-label clinical trial in patients with nephrotic range proteinuria who fail to respond to 4 weeks of oral prednisone and who are found to have FSGS on renal biopsy. Patients will be assigned to receive daily prednisone (60 mg/m2) for 3 months followed by either alternate day prednisone (40 mg/m2) for the ensuing 15 months or tacrolimus plus low-dose alternate day (10 mg/m2) for 18 months. In addition, patients will receive optimal doses of losartan and atorvostatin to control proteinuria, hypertension, and hypelipidemia. The primary outcome indicators will be: complete or partial remission of proteinuria, preservation of glomerular filtration rate, and prevention of renal scarring. Secondary outcome indicators will include correlation of response with a novel histopathologic classification, assessed by a centrol core pathology group. The study design will incorporate collection and storage of potentially important biological samples at the direction of the Data Coordinating Center and the Steering Committee of the NIDDK. The Eastern Regional Group for the Study of Focal Segmental Glomerulosclerosis in Children will be comprised of 41 sites under the direction of the Regional Coordinating Center at Montefiore Medical Center of the Albert Einstein College of Medicine. This project is expected to: 1) improve the outcome of children with FSGS, and, 2) create a nationwide network of clinical investigators that will facilitate future basic and clinical research in the field of pediatric nephrology, in general, and FSGS, in particular.

描述（由申请人提供）： 局灶节段性肾小球硬化症（FSGS）是儿童慢性肾脏病的主要原因。这种肾小球病变在少数人群中更为常见，并且经常在移植的肾脏中复发。尽管在分子遗传学方面取得了特别的进展，但这种情况的病因和最佳治疗方法仍然不明确。针对成人 FSGS 的非对照研究支持长期使用泼尼松治疗。儿童的初步数据表明，钙调神经磷酸酶抑制剂他克莫司可能对其他疗法耐药的患者有效。这项多中心研究的目的是比较他克莫司与强化泼尼松治疗在预防原发性 FSGS 进展方面的相对疗效。这是对这两种有前景的 FSGS 儿童疗法的首次对照评估。我们提议对患有肾病范围蛋白尿的患者进行一项随机、开放的临床试验，这些患者对口服泼尼松 4 周无效且肾活检发现患有 FSGS。患者将被分配每天接受泼尼松 (60 mg/m2) 治疗 3 个月，然后在接下来的 15 个月内隔日接受泼尼松 (40 mg/m2) 治疗，或在接下来的 18 个月内接受他克莫司加低剂量隔日治疗 (10 mg/m2)。此外，患者将接受最佳剂量的氯沙坦和阿托伐他汀来控制蛋白尿、高血压和高脂血症。主要结果指标是：蛋白尿完全或部分缓解、肾小球滤过率保持以及预防肾疤痕形成。次要结果指标将包括反应与新的组织病理学分类的相关性，由中心核心病理学小组评估。该研究设计将在数据协调中心和 NIDDK 指导委员会的指导下纳入潜在重要生物样本的收集和储存。儿童局灶节段性肾小球硬化症研究东部区域小组将由 41 个研究中心组成，由阿尔伯特·爱因斯坦医学院蒙特菲奥里医疗中心区域协调中心领导。该项目预计将：1) 改善 FSGS 儿童的治疗结果，2) 创建一个全国性的临床研究人员网络，以促进儿科肾病学领域（特别是 FSGS）未来的基础和临床研究。