Comparison of Intravenous Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Proliferative Lupus Nephritis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Assessment of Primary Renal Response
研究概览
简要总结
This study will be conducted to find out whether low dose or high dose cyclophosphamide therapy is effective in the treatment of proliferative lupus nephritis.It will also compare the side effects and risks of infection in low dose and high dose cyclophosphamide group. Half of the participants will receive a low dose cyclophosphamide for 3 months and half will receive high dose cyclophosphamide therapy monthly for 6 months followed by azathioprine 2 mg/kg.
详细描述
The study will be conducted at the Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER). Once the patients are diagnosed to have systemic lupus erythematosus (SLE) lupus nephritis and they satisfy the inclusion criteria , they will be informed about the nature and severity of the disease and about the expected treatment options and the duration of treatment. After providing written informed consent, eligible patients will be stratified into two groups. Block randomization will be done to generate random allocation sequence.They will receive either a low dose or high dose Cyclophosphamide as per the protocol mentioned below:
Group I : Low dose arm : Intravenous cyclophosphamide fixed pulse 500 mg each 2 weekly total 6 doses followed by azathioprine 2 mg/kg.
Group II : High Dose arm : Intravenous cyclophosphamide therapy 750 mg/m2 will be given every 4 weekly for total 6 doses followed by azathioprine 2 mg/kg.
Intravenous methylprednisolone pulses 1 gm each will be given for 3 days in both the treatment arms followed by prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks.
Additional drugs as per indication like hydroxychloroquine, antihypertensives and cotrimoxazole prophylaxis shall also be given unless contraindicated.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of SLE according to the American College of Rheumatology (ACR) criteria
- •Age >16 years
- •Proteinuria ≥500 mg in 24 hours/ urine routine microscopy showing active cellular casts/sediments.
- •Biopsy-proven proliferative lupus glomerulonephritis of class III, IV according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.
排除标准
- •Patients ever treated previously with intravenous or oral cyclophosphamide or received steroids >15mg/day in the last 3 months.
- •Patients with renal thrombotic microangiopathy, preexisting chronic renal failure, pregnancy, previous malignancy (except skin and cervical intraepithelial neoplasia), diabetes mellitus or coronary heart disease.
- •Patients with previously documented severe toxicity to immunosuppressive drugs.
- •Patients with acute/chronic infections.
研究组 & 干预措施
Low dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 500 mg intravenous 2 weekly for 3 months followed by azathioprine 2 mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Cyclophosphamide (Drug)
Low dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 500 mg intravenous 2 weekly for 3 months followed by azathioprine 2 mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Azathioprine (Drug)
Low dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 500 mg intravenous 2 weekly for 3 months followed by azathioprine 2 mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Methylprednisolone (Drug)
High Dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 750mg/m2 intravenous 4 weekly for 6 months followed by azathioprine 2mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Cyclophosphamide (Drug)
High Dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 750mg/m2 intravenous 4 weekly for 6 months followed by azathioprine 2mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Azathioprine (Drug)
High Dose Cyclophosphamide
Intravenous Cyclophosphamide therapy 750mg/m2 intravenous 4 weekly for 6 months followed by azathioprine 2mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Assessment of Primary Renal Response
时间窗: 12 months
Renal response as by the EULAR guidelines will be evaluated at 12 months for low dose group and high dose cyclophosphamide group. Inactive urinary sediments defined by ≤5 red blood cells (RBC)/hpf, ≤5 white blood cells (WBC)/hpf and no cellular casts as per the American college of rheumatology (ACR) definition. 1. Complete Response (CR) with urine protein creatinine ratio(UPCR) \<0.5 gm and Normal (GFR \> 90 ml/min) or stable (\<10% deterioration from baseline if GFR was previously abnormal) renal function and inactive urinary sediments. 2. Partial Response(PR) , defined as ≥50% reduction in proteinuria to subnephrotic levels , normal (GFR \> 90 ml/min) or stable (\<10% deterioration from baseline if GFR was previously abnormal) renal function and inactive urinary sediments. 3. No Response : Patients will be classified as non responders if criteria for CR or PR are not met and or if they experience severe flare.
次要结局
- Assessment of adverse events(12 Months)
- Proportion of patients with Renal and Non renal disease flares(12 months)
研究者
Dr. Vir Singh Negi
Head of the department and Proffessor of Clinical Immunology
Jawaharlal Institute of Postgraduate Medical Education & Research