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临床试验/NCT02765789
NCT02765789已完成不适用

Immunoadsorption in Anti-glomerular Basement Membrane Glomerulonephritis; a Pilot Study

University Medical Center Groningen2 个研究点 分布在 1 个国家目标入组 8 人开始时间: 2016年6月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
8
试验地点
2
主要终点
Number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units.

研究概览

简要总结

Anti-glomerular basement membrane (GBM) glomerulonephritis is a rare autoimmune disease mediated by anti-GBM antibodies and characterized by acute renal failure due to diffuse crescentic glomerulonephritis. Established treatment is cyclophosphamide and corticosteroids to suppress anti-GBM production and daily plasma exchange to remove circulating anti-GBM antibodies. The vast majority of patients with anti-GBM glomerulonephritis develop irreversible end-stage renal failure despite this treatment. Immunoadsorption may lower anti-GBM titres more effectively than plasma exchange. The goal of this interventional open, non-randomized pilot study is to study the efficacy, adverse events, logistic feasibility and costs of immuno-adsorption for the removal of anti-GBM antibodies in patients with acute renal failure due to anti-GBM glomerulonephritis. Eight patients with acute renal failure due to anti-GBM glomerulonephritis with or without accompanying pulmonary involvement will be treated with daily immunoadsorption, instead of plasma exchange, until anti-GBM titres are undetectable. All other aspects of the treatment (e.g. immunosuppressive treatment, renal replacement therapy) will be standard. The primary study parameter is the number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units. Secondary study parameters are the tolerability and adverse events of immunoadsorption, the logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment and costs of immunoadsorption.

详细描述

Rationale: Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare organ-specific autoimmune disease that is mediated by anti-GBM antibodies. It is characterized by acute renal failure due to diffuse crescentic glomerulonephritis, often accompanied by pulmonary hemorrhage. Established treatment is cyclophosphamide and corticosteroids to suppress anti-GBM production and daily plasma exchange to remove circulating anti-GBM antibodies. The vast majority of patients with anti-GBM glomerulonephritis develop irreversible end-stage renal failure despite this treatment. The treatment goal in anti-GBM glomerulonephritis is to achieve undetectable anti-GBM titres as rapid as possible. Immunoadsorption is an extracorporeal technique that selectively removes antibodies and may lower anti-GBM titres more effectively than plasma exchange. With this technique the patient's plasma is passed through an immunoadsorption column that contains protein A that binds antibodies of the IgG class like anti-GBM antibodies. However, data on the efficacy of anti-GBM removal by immunoadsorption compared with plasma exchange are scarce. In the literature, there are only a few case descriptions of the clinical effect of immunoadsorption in patients with anti-GBM disease with some cases showing recovery of renal function despite unfavourable prognosis (serum creatinine >500 µmol/l and/or high percentage of crescents on renal biopsy). Immunoadsorption is presently not used in the Netherlands for anti-GBM disease.

Objective: To study the efficacy, adverse events, logistic feasibility and costs of immuno-adsorption for the removal of anti-GBM antibodies in patients with acute renal failure due to anti-GBM glomerulonephritis.

Study design: Interventional, open, non-randomized, pilot study. After informed consent, patients will be treated according to the current treatment protocol with the exception of daily immunoadsorption instead of daily plasma exchange.

Study population: 8 patients with acute renal failure due to anti-GBM glomerulonephritis with or without accompanying pulmonary involvement.

Intervention: Participating patients will be treated with daily immunoadsorption (2.5 times the plasma volume), instead of plasma exchange, until anti-GBM titres are undetectable. All other aspects of the treatment (e.g. immunosuppressive treatment, renal replacement therapy) will be standard.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
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

入选标准

  • Acute renal failure due to anti-GBM glomerulonephritis with or without pulmonary involvement. Eligible patients must have a clinical picture met rapidly progressive glomerulonephritis in combination with one of the following:
  • Serological evidence of circulating anti-GMB antibodies (Dotblot, Phadia, ELISA). Patients with dual autoantibody positivity (anti-GBM antibodies and ANCA) can participate in this study.
  • Renal biopsy with necrotising glomerulonephritis with linear fluorescence for IgG along the GBM.

排除标准

  • Pregnancy

结局指标

主要结局

Number of days that anti-GBM antibody titre is above a toxic level, defined as >30 ELISA units.

时间窗: 60 days after study start

Nr of Days that anti-GBM title is \>30 units

次要结局

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(60 days after study start)
  • Logistic feasibility defined as the time interval between diagnosis and start of first immunoadsorption treatment.(60 days)
  • Costs of immunoadsorption (personnel and materials).(60 days)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

dr. C.F.M. Franssen

Nephrologist

University Medical Center Groningen

研究点 (2)

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