COOPERATIVE CLINICAL TRIALS IN RENAL TRANSPLANTATION

肾移植的合作临床试验

• 批准号: 3547801
• 负责人: J THOMAS ROSENTHAL
• 金额: $ 29.09万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3547801
• 关键词: acute renal failure; adult human (21+); blood chemistry; child (0-11); clinical trials; cooperative study; cyclosporines; dosage; drug adverse effect; drug screening /evaluation; drug tolerance; human subject; human therapy evaluation; hypertension; immunosuppression; immunosuppressive; insulin dependent diabetes mellitus; kidney function; kidney transplantation; macrolide antibiotics; magnetic resonance imaging; neoplasm /cancer; opportunistic infections; pharmacokinetics; renal toxin; steroids; transplantation immunology; urinalysis

The purpose of this project is to test the efficacy and safety of the new immune suppressive agent FK506 as baseline immune suppression in adult and pediatric cadaver renal transplants to attempt to improve the results in kidney transplantation over results currently obtained with conventional Cyclosporine based immune suppression. This will be accomplished by a randomized, open labeled, controlled clinical trial comparing standard Cyclosporine with FK506 based immune suppression. Both groups will receive steroid with an identical regimen. Rejection will be treated in a similar fashion in both groups with bolus steroids and OKT3. Primary outcome variables will be graft and patient survival one and two years after transplantation. Patients will be followed out to five years to determine long term safety. Detection and diagnosis of rejection will be facilitated by fine needle aspiration, core biopsy, and measurement of peripheral and intragraft cytokines. Studies will be carried out to attempt to refine the diagnostic accuracy of fine needle aspiration by use of DNA applification of individual lymphocytes to detect intragraft immune activation. Pharmacokinetic studies of FK506 will enable precise therapeutic dose ranges to be developed. Important secondary outcome variables will be compared. These include drug nephrotoxicity, hypertension, incidence of opportunistic infections, hyperlipidemia, diabetogenesis, growth in children, and compliance. Standard measurements of renal function will be augmented by NMR examination of kidneys prior to implantation, fine needle aspiration to quantitate degrees of tubular damage, and isotope scans to more precisely quantitate kidney function. After one year post transplant a steroid withdrawal protocol will be instituted in a group of patients with stable renal function to determine if FK506 is potentially more steroid sparing than Cyclosporine. Patients will be closely monitored for evidence of acute rejection prior to institution. In vitro measurements of immune functioning will be carried out simultaneously to attempt to predict which patients can prospectively be safely steroid withdrawn. If the results of the randomized trial show a superiority of FK506, then further refinements of its use will be developed, or it will be tested against newer drugs. Depending on the degree of improvement living related recipients will be included in such trials in the fourth and fifth years. If there is not a significant improvement with FK506, then newer drugs which are currently in animal development in our laboratories will be tested against Cyclosporine.

该项目的目的是测试新药物的功效和安全性 免疫抑制剂 FK506 作为成人和儿童的基线免疫抑制 儿科尸体肾移植尝试改善结果 肾移植优于目前传统肾移植的结果 基于环孢菌素的免疫抑制。 这将通过一个 比较标准的随机、开放标记、对照临床试验 环孢素与基于 FK506 的免疫抑制。 两组都将获得 具有相同治疗方案的类固醇。 拒绝将会以类似的方式处理 两组均采用推注类固醇和 OKT3。 主要结果变量是移植物和患者存活率一和二 移植后数年。 患者将被随访五年 以确定长期安全性。 排斥反应的检测和诊断将 通过细针抽吸、核心活检和测量来促进 外周细胞因子和移植物内细胞因子。 将进行研究 尝试通过使用细针抽吸来提高诊断准确性 应用个体淋巴细胞 DNA 检测移植物内免疫 激活。 FK506 的药代动力学研究将实现精确的 治疗剂量范围有待开发。 将比较重要的次要结果变量。 这些包括药物 肾毒性、高血压、机会性感染的发生率、 高脂血症、糖尿病发生、儿童生长和依从性。 核磁共振将增强肾功能的标准测量 植入前进行肾脏检查，细针穿刺 定量肾小管损伤程度，同位素扫描更精确 量化肾功能。 移植后一年后，将进行类固醇戒断方案 在一组肾功能稳定的患者中进行研究以确定 如果 FK506 可能比环孢素更节省类固醇。 患者 在使用前将密切监测急性排斥反应的证据 机构。 将进行免疫功能的体外测量 同时尝试预测哪些患者可以前瞻性地 安全地撤除类固醇。 如果随机试验的结果显示 FK506 具有优越性，那么 将开发其使用的进一步改进，或者将对其进行测试 对抗新药。 取决于生活相关的改善程度 受助者将在第四年和第五年参与此类试验。 如果 FK506 没有显着改善，则使用更新的药物 目前正在我们实验室进行动物开发的 针对环孢菌素进行了测试。