Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis During the Induction of Remission Period-EUROLUPUS vs. RITUXILUP Regimen: A Randomized Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of participants with a histological remission
研究概览
简要总结
The aim of the study is to evaluate the efficacy of a therapeutic regimen which decreases glucocorticoid exposure compared with standard therapy in patients with proliferative lupus nephritis during remission induction by evaluating the histological and clinical remission.
详细描述
After an initial screening phase during which a first kidney biopsy is performed, all patients that meet the inclusion criteria will be randomized to one of the treatment arms:
- EUROLUPUS regimen: 3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.
- RITUXILUP regimen: 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.
Second kidney biopsy will be performed 6 months after the start of the treatment phase.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of the patient between 18 and 80 years,
- •Patients diagnosed with systemic lupus erythematosus according to ACR 1997 or SLICC-2012 criteria
- •Diagnosis of proliferative lupus nephritis class III, IV +/- V (confirmed by renal biopsy and classified according to ISN / RPS);
- •Estimated glomerular filtration rate by CKD-EPI> 30 ml / min / 1.73 sqm
- •Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm but> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score) <6
- •Absence of contraindications to the use of Methylprednisolone, Mycophenolate mofetil, oral corticosteroids or Rituximab
- •Ability to provide informed consent
排除标准
- •The patient's age under 18 years
- •Patients with life-threatening complications (e.g. Cerebritis)
- •Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm
- •Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm but> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score)> 6
- •Presence of pregnancy / lactation
- •Patients who have received more than 2 g of Methylprednisolone intravenously in the last 4 weeks
- •Use in the last 3 months of biological therapy
- •Use of intravenous immunoglobulins / plasmapheresis in the last 6 months
- •The presence of an active infection
- •History of neoplasia
- •Comorbidities requiring systemic corticosteroid therapy
- •Non-adhesion
研究组 & 干预措施
RITUXILUP regimen
- 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.
干预措施: Rituximab (Drug)
RITUXILUP regimen
- 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.
干预措施: Mycophenolate Mofetil (Drug)
EUROLUPUS regimen (Standard therapy)
3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.
干预措施: Cyclophosphamide (Drug)
EUROLUPUS regimen (Standard therapy)
3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Percentage of participants with a histological remission
时间窗: 6 months
The primary endpoint is to evaluate the histologic remission at 6 months after initiation of induction treatment assessed by the change in the individual active lesions and in the activity modified NIH score.
次要结局
- Percentage of participants with a complete renal response(12 months)
- Percentage of patients with severe infectious episodes effects(24 months)
- The proportion of patients who obtained a complete renal response(6, 18 and 24 months)
- The proportion of patients who obtained a partial renal response(6, 12, 18, 24 months)
- Cumulative exposure to glucocorticoids(24 months)
- The proportion of patients who have developed relapse(24 months)
- Percentage of patients with severe non-infectious adverse events(24 months)
- Proportion of patients who showed normalization of complement fractions C3, C4 and negative anti-dcDNA antibodies at week 52(52 weeks)
- Percentage of patients with non-severe infectious episodes(24 months)
- Proportion of patients with progression of chronicity score by more than 2 units(6 months)
- Percentage of patients with non-severe non-infectious adverse events(24 months)
研究者
Bogdan Obrisca
Assist. Prof.
Institutul Clinic Fundeni