Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome Unresponsive to 8 Weeks of High Dose Prednisone
试验速览
- 阶段
- 3 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Complete remission
研究概览
简要总结
This will be an open-label, randomized controlled trial which compares continued treatment with high dose prednisone (standard therapy) to treatment with rituximab in patients with minimal change disease or focal segmental glomerulosclerosis unresponsive to 8 weeks of high dose prednisone .
patients either receive 2 doses of Rituximab 375 mg/m2 iv at time 0 and 14 days with termination of prednisone or standard therapy which consist of 8 additional weeks of high dose prednisone treatment.
详细描述
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are important causes of idiopathic nephrotic syndrome. First-line treatment with high dose prednisone up to 16 weeks is associated with serious side effects. Especially if treatment continues for more than 8 weeks.
Retrospective studies suggested that Rituximab may be more effective in patients unresponsive to 8 weeks of high dose prednisone. Treatment with rituximab was associated with a higher proportion of patients attaining remission of proteinuria and with fewer side effects.
This will be an open-label, randomized controlled trial which compares continued treatment with high dose prednisone (standard therapy) to treatment with rituximab in patients with an idiopathic nephrotic syndrome due to biopsy proven MCD or FSGS age 18 years or older.
All patients will be treated with high dose prednisone (1 mg/kg/day) for 8 weeks.
Patients can be included in the trial in case of persistent persistent proteinuria ≥ 2 g/ 24 hours or a protein-to-creatinine ratio ≥ 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone
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
- •Persistent proteinuria ≥ 2 g/ 24 hours or a protein-to-creatinine ratio ≥ 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone 1 mg/kg/day (max 80 mg/day)
- •Idiopathic nephrotic syndrome caused by biopsy proven minimal change disease or focal segmental glomerulosclerosis
排除标准
- •Severe nephrotic syndrome with hypotension
- •Previous treatment with immunosuppressive medication other than prednisone
- •Treatment with prednisone > 10 weeks in last six months
- •Secondary form of FSGS or minimal change disease
- •Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc).
- •Patients infected with HIV or suffering from other active infections
- •Patients inoculated with a vaccine within 4 weeks prior to inclusion
- •Pregnancy, breast feeding, women with inadequate contraception
- •Malignancy
- •Kidney transplantation
- •Previous treatment with monoclonal antibodies within 2 years prior to inclusion
- •Neutrophils < 1.5 x 109/L and/or platelet counts < 75 x 109/L
- •Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- •Active peptic ulcer
- •Known hypersensitivity to glucocorticoids
- •Insulin resistant diabetes mellitus
- •Treatment with carbamazepine, phenobarbital, phenytoin en rifampicin
- •Severe osteoporosis with vertebral fracture
研究组 & 干预措施
Rituximab
Rituximab: 375 mg/m2 intravenously on day 0 and day 14 B-cells will be monitored weekly, and if no complete depletion is achieved, additional dose(s) of Rituximab will be given at a weekly interval until complete B cell depletion (maximum of 2 additional doses).
干预措施: Rituximab (Drug)
Prednisone
Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks
干预措施: Prednisone (Drug)
结局指标
主要结局
Complete remission
时间窗: 8 weeks
The proportion of patients reaching complete remission defined as proteinuria \<0.3 g/day or \< 300 mg/g
次要结局
- Partial remission(8 weeks)
- Late complete or partial remission(2-12 months)
- Benefit-risk ratio 1(at 2 and 12 months)
- Time to remission(12 months)
- Time to relapse(12 months)
- Proportion of patients with a relapse(12 months)
- Proportion of patients treated with additional immunosuppressive drugs(12 months)
- General health assessment(at 2, 6, 9 and 12 months)
- Quality of life measured with TAAQOL(at 2, 6, 9 and 12 months)
- Benefit-risk ratio 2(at 2 and 12 months)
- Proportion of patients with adverse events(at 2 and 12 months)
- Cost-effectiveness analysis(at 2, 6, 9 and 12 months)
- Cost-utility analysis(at 2, 6, 9 and 12 months)
- Difference in kidney function(at 2 and 12 months)
- Proportion of patients with an increase of baseline serum creatinine ≥ 50%(at 2 and 12 months)