Personalized Medicine for Membranous Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 19
- 主要终点
- Clinical remission will be defined as a composite criterion combining (KDIGO definitions)
研究概览
简要总结
Randomized, open label, multicentre (20 sites), prospective trial comparing the efficacy of two therapeutic strategies to obtain clinical remission 1 year after diagnosis of Idiopathic Membranous Nephropathy with nephrotic syndrome and anti-PLA2R1 (phospholipase A2 receptor 1) antibodies:
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GEMRITUX protocol: 6 months of symptomatic antihypertensive and antiproteinuric therapy, and if the nephrotic syndrome persists at month-6 (urinary protein/creatinine ratio (UPCR) remains > 3.5 g/g and albuminemia < 30 g/l), two 375 mg/m2 rituximab infusions at 1-week interval.
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Personalized treatment:
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restricted anti-CysR activity at inclusion : 6-month symptomatic antihypertensive and antiproteinuric treatment (KDIGO)
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restricted anti-CysR activity after 6 months of symptomatic treatment with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 375 mg/m2 rituximab infusions at 1-week interval;
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Anti-CTLD (C-type lectin domains ) 1/7 activity at inclusion or after 6 months with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 1g rituximab infusions at 2-week interval at month 0 and/or month 6.
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
- •Age 18 years or more
- •Anti-PLA2R1 activity detected by ELISA or Euroimmune Immunofluorescence Assay
- •Nephrotic syndrome defined by proteinuria > 3.5 g/24h (or UPCR > 3.5 g/g) and serum albumin < 30 g/L at diagnosis
- •eGFR (CKD-EPI) > 30 ml/min/1,73 m2 at diagnosis
- •Symptomatic treatment according to KDIGO guidelines: maximal tolerated dose of NIAT : Non Immunosuppressive Antiproteinuric Treatment (angiotensin-converting enzyme inhibitor and/or angiotensin 2 receptor blockers, diuretics and statins)
- •Medical insurance
- •Signed informed consent
- •Having understood and accepted the need for long-term medical follow-up
- •Woman of child-bearing age must be using an effective method of contraception
排除标准
- •Secondary Membranous Nephropathy: Membranous Nephropathy related to cancer, infectious, systemic lupus erythematosis, drug
- •Anti-PLA2R1 antibodies not confirmed by central analysis (in this case the patient will be replaced)
- •Pregnancy or breastfeeding
- •Immunosuppressive treatment in the 3 last months
- •Cancer under treatment
- •Patient with complicated nephrotic syndrome that would require early immunosuppressive treatment (thrombosis, acute renal failure...)
- •Patients with active, severe infections or active hepatitis B
- •Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients
- •Patients in a severely immunocompromised state
- •Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- •Patients unable to give an informed consent
研究组 & 干预措施
Personalized treatment
- restricted anti-CysR activity at inclusion : 6-month symptomatic antihypertensive and antiproteinuric treatment (KDIGO)
- restricted anti-CysR activity after 6 months of symptomatic treatment with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 375 mg/m2 rituximab infusions at 1-week interval;
- Anti-CTLD1/7 activity at inclusion or after 6 months with persisting nephrotic syndrome (UPCR remains > 3.5 g/g and albuminemia < 30 g/l): two 1g rituximab infusions at 2-week interval at month 0 and/or month 6.
干预措施: Rituximab (Drug)
结局指标
主要结局
Clinical remission will be defined as a composite criterion combining (KDIGO definitions)
时间窗: 6 months
* Complete clinical remission: urinary protein/creatinine ratio (UPCR)\<0.3 g/g in spot morning urine samples and serum albumin \> 35 g/L and eGFR (epidermal growth factor receptor) \> 60 ml/min/1.73 m2 * Partial clinical remission: UPCR \< 3.5 g/g with a decrease greater than 50% from baseline and serum albumin \> 30 g/L and increase of serum creatinine lower than 20%
次要结局
- Immunological remission(6 months)