RAVE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。韦格纳肉芽肿病（WG）和显微多血管炎（MPA）是与抗中性粒细胞胞浆抗体（ANCA）相关的系统性血管炎的两种主要形式；统称为anca相关性血管炎（AAV）。AAV的常规治疗（环磷酰胺和糖皮质激素用于诱导缓解，然后硫唑嘌呤用于维持缓解）与治疗失败、疾病复发和毒性的高比例相关。AAV的潜在机制被认为是表达CD20抗原的致病性B细胞。用利妥昔单抗（一种CD20特异性单克隆抗体）（加上糖皮质激素）破坏这些B细胞可能恢复对ANCA抗原的耐受性并改善疾病。这是一项多中心、双盲、安慰剂对照试验，旨在确定利妥昔单抗（加糖皮质激素）与常规治疗相比对严重AAV的疗效和安全性。200名参与者将按1:1的比例随机分配到实验组或对照组。一般截止日期为最后一名参加者报名后18个月。考虑到30个月的招募期，试验治疗阶段的总持续时间为48个月。主要目的是确定利妥昔单抗（375 mg/m2，每周输注4次）和糖皮质激素在诱导缓解方面的疗效。其他目的包括比较治疗组之间的安全性、缓解持续时间和其他差异，以证明实验组的优越性，确定接受实验治疗的患者是否达到临床耐受性，并确定利妥昔单抗对炎症标志物和特异性免疫参数的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are the two major forms of systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA); collectively they are termed ANCA-associated vasculitis (AAV). Conventional therapy for AAV (cyclophosphamide and glucocorticoids for remission induction, then azathioprine for remission maintenance) is associated with a high percentage of treatment failures, disease relapses and toxicity. An underlying mechanism for AAV is thought to be pathogenic B cells that express the CD20 antigen. The destruction of these B cells with rituximab, a monoclonal antibody specific for CD20, (plus glucocorticoids) may restore tolerance to ANCA antigens and ameliorate disease. This is a multi-center, double-blind, placebo controlled trial to determine the efficacy and safety of rituximab (plus glucocorticoids) compared with conventional treatment for severe AAV. Two hundred participants will be randomized in a 1:1 ratio to the experimental arm or the control arm. The common closing date will be 18 months after the last participant is enrolled. Taking into account the recruitment period of 30 months, the total duration of the treatment phase of the trial will be 48 months. The primary objective is to determine the efficacy of rituximab (375 mg/m2, four weekly infusions) and glucocorticoids in the induction of remission. Other objectives include comparing the safety profiles, remission durations, and other differences between treatment groups, to demonstrate superiority of the experimental arm, to determine if patients who received the experimental therapy achieved clinical tolerance, and to determine the effect of rituximab on markers of inflammation and specific immune parameters.