Atlanta Sickle Cell Disease Clinical Research Consortium

描述(由申请人提供)： 镰状细胞病(SCD)临床研究网络(CRN)的RFA的目的是建立一个由15个临床中心组成的基础设施，这些中心将设计和执行多中心治疗试验，以改善镰状细胞疾病患者的健康状况。来自埃默里和莫尔豪斯医学院的临床研究人员提议在亚特兰大建立15个临床中心之一。该提案包括三个要素： 临床研究核心将为SCD CRN研究的设计和实施做出贡献，并在亚特兰大儿童保健和格雷迪卫生系统招收受试者。 项目1将验证这样的假设，即血管紧张素受体拮抗剂氯沙坦将降低镰状肾病患者肾脏疾病的进展速度。这一假设将在两组患者中进行验证：大量蛋白尿和临床肾病患者，以及微量蛋白尿患者。除了确定对进展性肾病的疗效外，这项研究还将比较长期服用氯沙坦和安慰剂对患有镰状细胞肾病的蛋白尿症患者的安全性和耐受性。 项目2是一项前瞻性的III期随机试验，旨在测试纳布芬在治疗SCD血管闭塞性疼痛方面优于吗啡的假设，因为患者将遭受较少的急性胸部综合征发作，并将因呼吸抑制和组胺释放减少而遭受较少的副作用。第二个假设是，高剂量自控镇痛配合低剂量镇痛剂输注优于低剂量自控镇痛配合高剂量自控镇痛。这一假设将通过一项四臂研究进行验证，该研究将吗啡与纳布芬进行比较，并对每种止痛剂进行低剂量持续输注与高剂量PCA的对比。 CRN的工作将对减少SCD并发症的发病率和死亡率做出重要贡献。拟议的两个项目将改善疼痛的治疗，疼痛是SCD最常见和致残的表现，并减轻慢性肾脏疾病的影响。(摘要结束)

DESCRIPTION (provided by applicant): The purpose of the RFA for a Sickle Cell Disease (SCD) Clinical Research Network (CRN) is to establish an infrastructure with 15 clinical centers that will design and perform multi-center therapeutic trials to improve health outcomes in persons with sickle cell disease. Clinical investigators from the Emory and Morehouse Schools of Medicine propose to establish one of the 15 clinical centers in Atlanta. The proposal includes three elements: The Clinical Research Core will contribute to the design and implementation of SCD CRN studies, and enroll subjects at Children's Healthcare of Atlanta and the Grady Health System. Project 1 will test the hypothesis that losartan, an angiotensin receptor antagonist, will reduce the rate of progression of renal disease in patients with sickle nephropathy. The hypothesis will be tested in two groups: patients with macroalbuminuria and overt nephropathy, and patients with microalbuminuria. In addition to determining the effect on progressive renal disease, the study will compare the safety and tolerability of losartan vs. placebo when administered long-term in albuminuric patients with sickle cell nephropathy. Project 2 is a prospective phase III randomized trial to test the hypothesis that nalbuphine is superior to morphine in the treatment of vaso-occlusive pain in SCD because patients will suffer fewer episodes of acute chest syndrome and will suffer fewer side effects because of less respiratory suppression and reduced release of histamine. A second hypothesis is that high-dose PCA with low-dose infusion of analgesic is superior to low-dose PCA with high-dose infusion. The hypothesis will be tested by a four-arm study that will compare morphine to nalbuphine and low-dose continuous infusion with high-dose PCA to high-dose infusion with low-dose PCA for each analgesic. The work of the CRN will contribute importantly to lessening morbidity and mortality from complications of SCD. Two proposed projects will improve treatment of pain, the most common and disabling manifestation of SCD and lessen the impact of chronic kidney disease. (End of abstract)