Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 704
- 试验地点
- 98
- 主要终点
- Composite of i) All-cause Mortality or ii) End-stage Renal Disease
研究概览
简要总结
The purpose of this study is to determine whether plasma exchange as well as immunosuppressive therapy are effective in reducing death and end-stage renal disease (ESRD). The trial will also study whether a reduced cumulative dosing regimen of glucocorticoids is as effective as a standard disease regimen.
The FDA-OOPD is one of the funding sources for this study.
详细描述
Granulomatosis with polyangiitis (Wegener's) (WG) and microscopic polyangiitis (MPA) are syndromes of primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA). Together, these syndromes are grouped as ANCA-associated systemic vasculitis (AAV).
Plasma exchange, a method of rapidly removing potentially pathogenic ANCA and other mediators of inflammation and coagulation, has shown promise as an adjunctive therapy in AAV to improve early disease control and improve rates of renal recovery in severe disease. Glucocorticoids (steroids) are a standard of care in the treatment of AAV. High doses of glucocorticoids early in disease, although reduce disease activity due to their anti-inflammatory and immunosuppressive properties, also increase the risk of infection, particularly in the elderly and in the presence of uremia. There is no randomized trial data to guide glucocorticoids dosing.
Patients with severe new or relapsing AAV and pulmonary hemorrhage and/or renal disease will be eligible for this trial.
Subjects participating in this study will be randomized to receive one of the following groups;
- Plasma exchange - 7 exchanges and, either standard or low-dose glucocorticoids or
- No plasma exchange and, either standard or low-dose glucocorticoids
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions
- •Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA
- •Severe vasculitis defined by at least one of the following:
- •Renal involvement characterized by both of the following:
- •Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria
- •eGFR <50 ml/min/1.73 m2
- •Pulmonary hemorrhage due to active vasculitis defined by:
- •A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)
- •The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection)
- •At least one of the following:
- •Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage
- •Observed hemoptysis
- •Unexplained anemia (<10 g/dL) or documented drop in hemoglobin >1 g/dL)
- •Increased diffusing capacity of carbon dioxide
- •Provision of informed consent by patient or a surrogate decision maker
排除标准
- •A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
- •Positive serum anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
- •Receipt of dialysis for >21 days immediately prior to randomization or prior renal transplant
- •Age <15 years
- •Pregnancy at time of study entry
- •Treatment with >1 IV dose of cyclophosphamide and/or >14 days of oral cyclophosphamide and/or >14 days of prednisone/prednisolone (>30 mg/day) and/or >1 dose of rituximab within the 28 days immediately prior to randomization
- •A comorbidity that, in the opinion of the investigator, precludes the use of cyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange
- •Plasma exchange in 3 months prior to randomization
研究组 & 干预措施
Plasma Exchange with Standard Glucocorticoids
Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose.
干预措施: Plasma Exchange (Procedure)
Plasma Exchange with Standard Glucocorticoids
Participants in this arm undergo plasma exchange and take a standard glucocorticoid dose.
干预措施: Glucocorticoids [Standard Dose] (Drug)
No Plasma Exchange with Standard Glucocorticoids
Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose.
干预措施: No Plasma Exchange (Other)
No Plasma Exchange with Standard Glucocorticoids
Participants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose.
干预措施: Glucocorticoids [Standard Dose] (Drug)
Plasma Exchange with Reduced-Dose Glucocorticoids
Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose.
干预措施: Plasma Exchange (Procedure)
Plasma Exchange with Reduced-Dose Glucocorticoids
Participants in this arm undergo plasma exchange and take a reduced glucocorticoid dose.
干预措施: Glucocorticoids [Reduced Dose] (Drug)
No Plasma Exchange with Reduced-Dose Glucocorticoids
Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose.
干预措施: No Plasma Exchange (Other)
No Plasma Exchange with Reduced-Dose Glucocorticoids
Participants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose.
干预措施: Glucocorticoids [Reduced Dose] (Drug)
结局指标
主要结局
Composite of i) All-cause Mortality or ii) End-stage Renal Disease
时间窗: Time frame varied by subject: minimum of 1 year - maximum of 7 years
The primary outcome was a composite of death from any cause or end-stage renal disease (ESRD), defined as ≥12 continuous weeks of renal replacement therapy.
次要结局
- Number of Participants With Sustained Remission(Time frame varied by subject: minimum of 1 year - maximum of 7 years)
- Health-related Quality of Life Using the SF-36 Physical Composite(12 months)
- Health-related Quality of Life Using the SF-36 Mental Composite(12 months)
- Rate of Serious Infection Events(Time frame varied by subject: minimum of 1 year - maximum of 7 years)
- Health-related Quality of Life Using the EQ-5D Index Descriptive System(12 months)
研究者
Peter Merkel
Professor
University of Pennsylvania