Comparison of Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment for ANCA Repositivation in Granulomatosis With Polyangiitis and Microscopic Polyangiitis: a Prospective, Multicenter, Randomized Controlled Study.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Survival without relapse in each arm at 24 months. (relapse defined by The Birmingham Vasculitis Activity Score (BVAS) score > 0)
研究概览
简要总结
The PREP-ANCA study seeks to establish a more personalized treatment strategy for ANCA-associated vasculitides by assessing the efficacy of pre-emptive rituximab administration upon ANCA repositivity in preventing relapses in granulomatosis with polyangiitis and microscopic polyangiitis.
详细描述
Treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) is currently based on an induction phase aimed at achieving remission, followed by a maintenance phase to prevent relapse. Rituximab is considered a cornerstone of maintenance therapy, typically administered for a minimum of 18 months. However, the extension of rituximab treatment beyond this period remains debated, primarily due to the increased risk of infections associated with prolonged immunosuppression.
The use of biomarkers to guide treatment duration-extending therapy only in patients at high risk of relapse-represents a promising step toward personalized management. Among the potential biomarkers, ANCA (anti-neutrophil cytoplasmic antibodies) have emerged as a particularly attractive candidate, having been identified as an early marker of relapse. Early studies on pre-emptive immunosuppressive strategies have suggested that timely intervention could reduce relapse rates; however, none of these studies were conducted in the rituximab era. As a result, in the absence of a dedicated prospective randomized trial, current recommendations advise close monitoring in the event of isolated ANCA repositivity in patients who remain in clinical remission.
The objective of this study is to determine whether pre-emptive rituximab administration upon ANCA repositivity is superior to current standard care in reducing the risk of relapse.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged ≥ 18 years
- •Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria
- •Maintenance treatment with rituximab for at least 18 months, administered as follows: a 500 mg infusion on day 1 (with an optional repeat dose on day 15), followed by 500 mg infusions every 6 months for a total of 4 to 5 doses
- •Patient in complete remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 at the time of randomization
- •ANCA repositivity (confirmed by antigen-specific testing) within the 3 months prior to randomization
- •Ability to provide written informed consent prior to participation
- •Affiliation to a national health insurance or social security scheme
排除标准
- •Diagnosis of any vasculitis other than GPA or MPA
- •Active disease relapse, defined as BVAS > 0
- •Acute active infection requiring hospitalization or intravenous anti-infective therapy within 4 weeks prior to screening, or oral anti-infective treatment within 2 weeks prior to screening
- •History of deep tissue infections (e.g., fasciitis, abscess, osteomyelitis, septic arthritis) within 12 months prior to inclusion
- •History of severe, chronic, or recurrent infections, or any underlying condition predisposing the patient to serious infections
- •Administration of a live vaccine within 4 weeks prior to study inclusion
- •Active malignancy or history of hematologic malignancy within the past 5 years, except for localized prostate cancer or basal cell carcinoma of the skin
- •Presence of systemic diseases for which the study treatments may have unpredictable or inappropriate consequences
- •History of severe allergic or anaphylactic reactions, or known hypersensitivity to humanized or murine monoclonal antibodies and/or corticosteroids
- •Known hypersensitivity to any monoclonal antibody or biologic agent
- •Patients previously deemed non-responders or failures to rituximab therapy
- •Suspicion of poor adherence to treatment or anticipated inability or refusal to comply with the required follow-up visits and procedures
- •Inability or refusal to provide written informed consent Pregnant or breastfeeding women. Women of childbearing potential must use effective contraception during the study and for 6 months after the last infusion. Breastfeeding is contraindicated during treatment and for 6 months following the final rituximab dose.
研究组 & 干预措施
Rituximab
Rituximab 500 mg administered intravenously (IV) every 6 months for a total duration of 18 months, depending on ANCA positivity.
干预措施: Rituximab (Drug)
Control
Standard care follow up
结局指标
主要结局
Survival without relapse in each arm at 24 months. (relapse defined by The Birmingham Vasculitis Activity Score (BVAS) score > 0)
时间窗: 24 months.
The BVAS is the most effective validated tool for documenting disease activity. It provides valid definitions of remission and response to treatment, as well as suggestions.
次要结局
- Number of participants with a major or a minor relapse during the study.(48 months)
- Number of adverse events(48 months)
- Number of serious adverse events such as potentially fatal, requiring hospitalisation, causing significant disability or resulting in death(48 months)
- Numbers of rituximab perfusions performed in each arms.(48 months)
- The index of damage caused by vasculitis according to the Vasculitis Damage Index (VDI)classification during follow-up(48 months)
- Quality of life according to Health Assessment Questionnaire (HAQ ) classifications during follow-up(48 months)
- Quality of life according to SF-36 classifications during follow-up(48 months)
- Mortality in each arm(48 months)
- Cumulative dose and duration of corticosteroid treatment in each arm(48 months)
- Evolution of ANCA levels and CD19+ B-lymphocyte in each study arm and their correlation with clinical events(48 months)