Thymectomy in non-thymomatous MG patients on Prednisone

接受泼尼松治疗的非胸腺瘤型 MG 患者的胸腺切除术

• 批准号: 7125501
• 负责人: JOHN NEWSOM-DAVIS
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-24 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125501
• 关键词: cholinergic receptors; clinical research; clinical trials; combination therapy; cooperative study; human subject; human therapy evaluation; musculoskeletal disorder therapy; myasthenia gravis; nervous system disorder therapy; neuromuscular disorder chemotherapy; patient oriented research; prednisone; thymectomy

DESCRIPTION (provided by applicant): Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85% of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission and can cause severe, sometimes life-threatening, weakness. Thymectomy has been used world-wide to treat non-thymomatous MG, based on retrospective non-randomized studies. Prednisone (a corticosteroid) is also frequently used to treat MG. Both therapies are often employed together and both have adverse effects. Whether thymectomy benefits those who are also receiving prednisone is not known. To investigate the safety while comparing efficacy, we propose a multicenter, multiracial, international, single-blinded, 3-year duration clinical trial in which patients aged 18-60 years with generalized AchR-Ab positive non- thymomatous MG are randomized to receive extended transsternal thymectomy (ETTX) or no thymectomy. Both groups will receive prednisone administered by a 'blind' evaluator according to the same set protocol aimed at establishing the minimum dose needed to achieve and maintain Minimal Manifestation (MM) status. The primary endpoint will comprise response and toxicity using a composite measuring clinical course, short and long term toxicities based on: (a) clinical efficacy of therapy evaluated by the QMG weakness score (b) frequency of serious adverse events (c) the total dose of prednisone (Area under the Dose time Curve, AUDTC). A significant difference favoring ETTX would establish its clinical benefits in this patient population, and provide indirect evidence of the possible benefits of ETTX in patients not receiving prednisone medication. Conversely, failure to demonstrate a significant difference in the global or individual components of the primary endpoint would suggest that thymectomy is an unnecessary procedure in the population studied. Subgroup analysis may show whether benefits are confined to those who are prednisone naive at entry or in a particular age group. Thus the results will impact on current clinical practice.

描述（由申请人提供）：重症肌无力（MG）是一种累及胸腺的自身免疫性疾病，其中85%的患者具有肌肉乙酰胆碱受体（AchR-Ab）抗体，该抗体干扰神经肌肉传递，可导致严重的，有时危及生命的虚弱。根据回顾性非随机研究，胸腺切除术已在世界范围内用于治疗非胸腺瘤性MG。泼尼松（一种皮质类固醇）也常用于治疗MG。这两种疗法经常一起使用，两者都有副作用。胸腺切除术是否有益于那些同时接受强的松治疗的患者尚不清楚。为了在比较疗效的同时研究安全性，我们提出了一项多中心、多种族、国际、单盲、持续3年的临床试验，其中年龄为18-60岁的全身AchR-Ab阳性非胸腺瘤性MG患者随机接受扩大经胸骨胸腺切除术（ETTX）或不接受胸腺切除术。两组都将接受泼尼松给药，由一名“盲态”评估者根据相同的方案给药，旨在确定达到和维持最小表现（MM）状态所需的最小剂量。主要终点将包括反应和毒性，使用基于以下的测量临床过程、短期和长期毒性的复合物：（a）通过QMG虚弱评分（B）严重不良事件的频率评价的治疗的临床功效（c）泼尼松的总剂量（剂量时间曲线下面积，AUDTC）。有利于ETTX的显着差异将确定其在该患者人群中的临床益处，并提供ETTX在未接受泼尼松药物治疗的患者中可能益处的间接证据。相反，未能证明主要终点的总体或个体组分存在显著差异表明胸腺切除术在研究人群中是不必要的手术。亚组分析可以显示益处是否仅限于那些在入组时或特定年龄组中未接受过泼尼松治疗的患者。因此，这些结果将影响当前的临床实践。