OPTIMAL IMMUNOSUPPRESSION IN RENAL TRANSPLANTATION

肾移植中的最佳免疫抑制

• 批准号: 6274017
• 负责人: STEPHEN R SMITH
• 金额: $ 2.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274017
• 关键词: azathioprine; biopsy; clinical research; clinical trials; combination chemotherapy; cyclosporines; human subject; human therapy evaluation; immunosuppression; immunosuppressive; kidney transplantation; prednisone

Triple immunosuppressant therapy with cyclosporine (CsA), prednisone, and either azathioprine or, more recently, mycophenolate mofetil (MMF) is used in most transplant centers for renal transplantation. These drugs have different mechanisms of action and different toxicities. It has been observed that many patients do well with only two immunosuppressant agents late after renal transplantation, however, there are no controlled comparative trials of the withdrawal of immunosuppressant agents. This is an open label, randomized, controlled, therapeutic comparison trial. All patients will be treated with standard maintenance immuno- suppression during the first year after transplantation. At 12 months patients will be receiving MMF (1 g bid), CsA, and prednisone. Patients will be randomly allocated to 3 groups. Enrollment will occur 12-15 months after renal transplantation and follow-up will be for 2 years for evaluation of renal function and 5 years for those patients who agree to undergo allograft biopsies at baseline and 5 years after withdrawal. Patients allocated to group I will undergo withdrawal of CsA over 12 weeks, patients in Group II will be taken off prednisone over 12 weeks and patients in group III will discontinue MMF. At the time of CsA cessation in Group I, prednisone will be increased to 40 mg qd for one week, 30 mg for one week, then returned to baseline. At 3 months after CsA cessation the prednisone will be further reduced to 7.5 mg qd or 15 mg qod. In Group II, the CsA target blood level will be reduced from 125-175 to 75-125 at 3 months after prednisone withdrawal. In Group III, the prednisone dosing will be the same as for group I, except that no flare of prednisone will be given when MMF is stopped.

环孢素(CsA)、泼尼松和 使用硫唑嘌呤或最近使用的霉酚酸酯(MMF) 在大多数肾移植中心。这些药有 不同的作用机制和不同的毒性。一直以来 观察到，许多患者只使用两种免疫抑制剂就能很好地发挥作用 然而，在肾移植后的晚期，并没有控制 免疫抑制剂停用的对比试验。 这是一项开放的标签，随机、对照、疗效比较 审判。所有患者都将接受标准维持免疫治疗- 移植后第一年内的抑制作用。在12个月时 患者将接受MMF(1g Bid)、CsA和泼尼松的治疗。病人 将被随机分配到3组。招生时间为12-15天 肾移植后几个月，随访时间为2年 对肾功能进行评估，并对同意的患者进行5年 在基线和停药5年后接受同种异体肾活检。 被分配到I组的患者将在12岁以上停用CsA 2周，II组患者将在12周内停用强的松，并 III组患者将停止使用MMF。在CSA停止时 I组强的松剂量增至40 mg，每日1次，共30 mg。 持续一周，然后回到基线水平。停用CsA后3个月 强的松将进一步减少到7.5 mg，qd或15 mg，qd。在……里面 II组，CsA目标血药浓度将由125-175降至 强的松停药后3个月75~125。在第三组， 泼尼松的剂量将与第一组相同，只是没有 当MMF停止时，将给予泼尼松。