Thymectomy in Non-Thymomatous MG Patients on Prednisone

接受泼尼松治疗的非胸腺瘤型重症肌无力患者的胸腺切除术

• 批准号: 6987046
• 负责人: GARY R CUTTER
• 金额: $ 138.64万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6987046
• 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）肌无力重症（MG）是一种自身免疫性疾病，涉及胸腺，其中85％的患者患有肌肉乙酰胆碱受体（ACHR-AB）抗体，会干扰神经肌肉的传播，并可能引起严重的，有时是生命的，弱点，弱点。基于回顾性非随机研究，胸腺切除术已被全世界用于治疗非心心理MG。泼尼松（皮质类固醇）也经常用于治疗Mg。两种疗法通常都被一起使用，并且都有不良影响。胸腔切除术是否使那些也接受泼尼松的人受益。为了在比较疗效的同时研究安全性，我们提出了一个多中心，多种族，国际，单盲，3年持续时间临床试验，其中18至60岁的患者患有广义ACHR-AB-AB阳性非胸腺膜肌Mg，以随机化以接受扩展的跨胸骨胸腔胸腔胸腔切除术（ETTX）或无胸腺切除术。两组将根据旨在确定实现和维持最小表现状态所需的最低剂量的同一集合协议，接受“盲目”评估者管理的泼尼松。主要终点将使用复合测量临床课程，短期和长期毒性基于以下基础：（a）通过QMG弱点评分（B）严重不良事件的频率评估治疗的临床疗效（c）pretnisone的总剂量（剂量时间曲线，AUDTC）。有利于ETTX的显着差异将在该患者人群中建立其临床益处，并提供间接证明ETTX在未接受泼尼松药物的患者中可能受益的益处。相反，未能证明主要终点的全球或个体成分存在显着差异，这表明胸腔切除术是所研究人群中不必要的程序。亚组分析可能表明，益处是否仅限于入境或特定年龄段的泼尼松的人。因此，结果将影响当前的临床实践。