Plasma Exchange and Glucocorticoids for Treatment of ANCA-Associated Vasculitis

血浆置换和糖皮质激素治疗 ANCA 相关性血管炎

• 批准号: 8537733
• 负责人: Peter A Merkel
• 金额: $ 46.61万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8537733
• 关键词: Plasma; Exchange; Glucocorticoids; Treatment; ANCA

DESCRIPTION (provided by applicant): Wegener's granulomatosis and microscopic polyangiitis are rare (combined prevalence <200,000 in U.S.), multi-system diseases commonly referred to as anti-neutrophil cytoplasm antibody (ANCA) -associated vasculitis (AAV). AAV, although rare, is almost universally fatal if left untreated. Modern treatment strategies utilize potent immunosuppressive medications and high doses of glucocorticoids (GC). While treatment has resulted in improved survival for patients with AAV, severe forms are still associated with unacceptably high rates of poor outcomes with up to 40% of patients reaching end-stage renal disease (ESRD) or death within 5 years of diagnosis. Poor outcomes in patients with AAV appear due to both inadequate disease control and as a result of treatment related toxicities and adverse events. The broad aim of this research is to improve ESRD and mortality rates for patients with AAV by improving the efficacy of treatment while reducing treatment-related adverse events. Plasma exchange, a method of removing potentially pathogenic antibodies, coagulation factors and inflammatory mediators has shown promise in improving outcomes for patients with AAV. High-dose GC during early treatment is associated with increased rates of serious infections, a principle cause of death in patients with AAV. This research will be achieved through two specific aims: 1) to conduct a multi-national randomized clinical trial comparing the use of adjunctive plasma exchange to standard treatment alone for AAV and 2) to conduct a multi-national randomized clinical trial of a low-dose GC regimen to a standard dose GC regimen for AAV. The addition of adjunctive plasma exchange is hypothesized to improve the efficacy of treatment in patients with AAV while the reduction in GC dose is hypothesized to reduce treatment related adverse events. These aims will be achieved in the context of a large, multinational, two-by-two factorial design randomized control trial in which investigators will be blinded to the GC regimen of patients. 500 will be recruited over 5 years and randomized in a 1:1 fashion to each intervention and followed for a minimum of 2 years (maximum 7) for the development of the primary outcome of ESRD or death. This application seeks funding to support 5 study sties in the United States and combine resources with funding from the United Kingdom.

描述（由申请人提供）： 韦格纳肉芽肿病和显微镜下多血管炎很罕见（在美国综合患病率<200,000），多系统疾病通常称为抗中性粒细胞胞质抗体（ANCA）相关血管炎（AAV）。 AAV 虽然罕见，但如果不及时治疗，几乎都会致命。现代治疗策略利用强效免疫抑制药物和高剂量的糖皮质激素 (GC)。虽然治疗提高了 AAV 患者的生存率，但严重形式的不良结局率仍然高得令人无法接受，高达 40% 的患者达到终末期肾病 (ESRD) 或在诊断后 5 年内死亡。 AAV 患者的预后不良是由于疾病控制不充分以及治疗相关的毒性和不良事件造成的。 这项研究的主要目标是通过提高治疗效果同时减少治疗相关的不良事件来改善 AAV 患者的 ESRD 和死亡率。血浆置换是一种去除潜在致病性抗体、凝血因子和炎症介质的方法，在改善 AAV 患者的预后方面显示出希望。早期治疗期间的高剂量 GC 与严重感染率增加有关，严重感染是 AAV 患者死亡的主要原因。这项研究将通过两个具体目标来实现：1）开展一项多国随机临床试验，比较辅助血浆置换与单独标准治疗 AAV 的使用；2）开展一项低风险的多​​国随机临床试验。将 GC 剂量方案调整为 AAV 的标准剂量 GC 方案。假设增加辅助血浆置换可以提高 AAV 患者的治疗效果，而减少 GC 剂量则可以减少治疗相关的不良事件。这些目标将在一项大型、跨国、2×2 析因设计随机对照试验的背景下实现，在该试验中，研究人员将对患者的 GC 方案不知情。将在 5 年内招募 500 名患者，并以 1:1 的方式随机分配到每次干预措施中，并随访至少 2 年（最多 7 年），以了解 ESRD 或死亡的主要结局。该申请寻求资金支持美国的 5 个研究机构，并将资源与英国的资金结合起来。