Randomized Trial of Plasma Exchange as Adjunctive Therapy for Severe Crescentic GlomerUlonephritis of IgA NEphropathy (RESCUE Study)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- End-stage renal disease or death
研究概览
简要总结
Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. This study will evaluate the efficacy and safety of plasma exchange as adjunctive therapy for severe crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.
详细描述
IgA nephropathy (IgAN) is one of the most common glomerulonephritides and is characterized by a highly variable clinical course and diverse histopathological lesions. Although most affected individuals develop chronic, slowly progressive renal injury, a subgroup of patients (<5% of all IgAN patients) with diffuse crescent formation, which is termed as crescentic IgA nephropathy (CreIgAN) and often leads to rapidly progressive kidney failure. The recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest high-dose steroids and cyclophosphamide therapy for CreIgAN. However, this suggestion is mainly based on several small observational studies, and the 1- and 5-year renal survival rates of patients treated with this regimen were as low as 65% and 28%, respectively, in one large cohort of CreIgAN patients. The efficacy of plasma exchange (PE) in severe CreIgAN is not well evaluated, although several anecdotal reports have indicated benefit of PE in combination with immunosuppressive therapies in IgAN patients. Retrospective cohort study in our unite also supported the benefit of PE as additional therapy for CreIgAN patients. However, randomized controlled trial is needed to evaluate the efficacy and safety of plasma exchange as adjunctive therapy for crescentic IgA nephropathy compared to pulse methylprednisolone on a background of oral prednisolone and cyclophosphamide in prevent kidney failure.
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
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven within 3ws
- •Primary IgAN or Henoch-Schönlein Purpura nephritis of crescent >50%(>8 glomeruli)
- •Serum creatinine ≥ 200 μmol/l， rapidly deterioration of renal function
排除标准
- •<14 or >65 years old
- •With high Scr requiring dialysis for≥ 3w
- •Scr>200μmol/L ≥1 yr before entry
- •Main of old crescent ; Fibrous crescent>50%
- •Anti-glomerular basement membrane (GBM) or antineutrophil cytoplasmic antibody (ANCA) antibody positive
- •Women in gestational and lactational period
- •With diabetes or uncontrollable malignant hypertension or Thrombotic Microangiopathy
- •With Malignancy
- •Chronic active infection including HBV hepatitis C virus (HCV) HIV or active tuberculosis
- •Other autoimmune disease
- •A second clearly defined cause of renal failure
- •Contraindication of plasma exchange treatment or steroid pulse
- •Patients who are unlikely to comply with the study protocol in the view of the treating physician.
研究组 & 干预措施
PE and methylprednisolone pulse
Plasma exchange(PE) and methylprednisolone pulse therapy: plasma exchange >7 within 3ws, Volume: 60ml/kg/course; Replacement fluid: 5% albumin or fresh frozen plasma and methylprednisolone pulse therapy Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month.
干预措施: Plasma Exchange (PE) (Procedure)
PE and methylprednisolone pulse
Plasma exchange(PE) and methylprednisolone pulse therapy: plasma exchange >7 within 3ws, Volume: 60ml/kg/course; Replacement fluid: 5% albumin or fresh frozen plasma and methylprednisolone pulse therapy Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month.
干预措施: Methylprednisolone pulse (Drug)
Methylprednisolone pulse
Methylprednisolone pulse alone: methylprednisolone 7-15mg/kg/d 3 times on consecutive or alternate days Basic treatment: Oral prednisone was tapered from 1 mg/kg/d for 6wks, then diminish 5mg/d every 10d, stop at the sixth month; cyclophosphamide 1.5 mg/kg/d for 3 months, 50mg /d at 3 months and stopped at 6 month.
干预措施: Methylprednisolone pulse (Drug)
结局指标
主要结局
End-stage renal disease or death
时间窗: 12 months after final subject is enrolled
End-stage renal disease: defined as a need for maintenance dialysis \> 6 months; or need kidney transplantation , and death; during follow-up.
次要结局
- Renal remission(12 months after final subject is enrolled)
- Proteinuria remission(At the 12th month and 36th month after randomization)
研究者
Hong Zhang
Professor, Principal Investigator
Peking University First Hospital