NCT02457221已完成3 期
A Phase III, Randomized, Open, Parallel-controlled, Multi-center Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 314
- 试验地点
- 35
- 主要终点
- Remission rate (complete remission + partial remission)
研究概览
简要总结
The objective of this study is to evaluate the efficacy and safety of Tacrolimus capsules for induction remission in patients with lupus nephritis, and compare the efficacy and safety with Cyclophosphamide injections.
详细描述
This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18.5≤Body Mass Index (BMI) <27;
- •Diagnosed as systemic lupus erythematosus (based on American Rheumatism Association Diagnostic Criteria 1997)
- •Diagnosed as III, IV, V, III + V, IV + V lupus nephritis (according to the LN classification in International Society of Nephrology and Renal Pathology Society (ISN/RPS) 2003) within 24 weeks before enrollment with renal biopsy;
- •24-hour urine protein ≥ 1.5g, Scr<260umol/L (or 3mg/dL)
排除标准
- •Class II or VI lupus nephritis or renal biopsy chronic index (CI) > 3 or with TMA;
- •Received immunosuppressants (mycophenolate mofetil (MMF), cyclosporine, methotrexate, mechlorethamine, chlorambucil, tripterygium preparations, leflunomide etc.) treatment with a duration of more than one week within 30 days prior to enrollment;
- •Received tacrolimus (except for topical use) or cyclophosphamide treatment within 30 days prior to enrollment;
- •Received a course of methylprednisolone (MP) pulse therapy or gamma globulin treatment or plasma exchange within 30 days prior to enrollment;
- •Patients with history of allergies to tacrolimus, cyclophosphamide or methylprednisolone;
- •Pregnancy, lactation or patient unwilling to take contraceptive measures;
- •Patients with estimated maintenance dialysis for more than eight weeks; or dialysis for more than two weeks prior to entering observation;
- •Patients received kidney transplantation or plan to have kidney transplantation recently;
- •Serum creatinine (Scr) ≥260umol/L (or 3mg/dL) or creatinine clearance rate (Ccr) < 30ml/(min.1.73m2); according to Cockcroft-Gault formula: Ccr (ml/sec) = [(140- age)× Weight (kg)] × K / [72×Scr (umol/L) ×0.6786], Female K = 0.85, Male K = 1.0;
- •Patients suffering from liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal lab value) or bilirubin more than 3 times the upper limit of normal lab value;
- •Patients diagnosed with diabetes;
- •History of gastrointestinal bleeding or pancreatitis within 3 months;
- •Uncontrollable hyperkalemia after dietary therapy or reduction of potassium treatment (exceed the upper limit of normal lab value);
- •Patients suffering from lupus pneumonia or lung injury;
- •Patients with anemia (hemoglobin <7g/dl) or bone marrow suppression (WBC <3.0×109/L, and/or neutrophils <1.5×109/L, and/or platelets <50×109/L) not secondary to systemic lupus erythematosus;
- •With congenital heart disease, arrhythmia, heart failure or other severe cardiovascular diseases;
- •With refractory hypertension (defined as blood pressure still exceeds 180/110 mmHg despite taking three different types of antihypertensive drugs [one of them is diuretic] simultaneously);
- •Patients with recurrent tumors within 5 years;
- •Severe infection that requires intravenous antibiotics within 2 weeks prior to enrollment;
- •Patients with infection of hepatitis B virus or hepatitis C virus; patients with active tuberculosis; patients with severe immunodeficiency diseases (including active cytomegalovirus infection (positive CMV IgM antibody), or human immunodeficiency virus (HIV) infection, etc.);
- •Patients with lupus encephalopathy or other life-threatening complication of systemic lupus erythematosus;
- •Patients participated in other clinical trials within three months before enrollment
研究组 & 干预措施
Tacrolimus group
Experimental
Tacrolimus capsules + steroid
干预措施: Tacrolimus capsules (Drug)
Tacrolimus group
Experimental
Tacrolimus capsules + steroid
干预措施: Prednisone (Drug)
Cyclophosphamide group
Active Comparator
Cyclophosphamide injections + steroid
干预措施: Cyclophosphamide injections (Drug)
Cyclophosphamide group
Active Comparator
Cyclophosphamide injections + steroid
干预措施: Prednisone (Drug)
结局指标
主要结局
Remission rate (complete remission + partial remission)
时间窗: at 24 weeks
complete remission: urine protein \< 0.5g/24hr, and serum albumin≥3.5g/dl, and stable renal function (Scr increase ≤ 15% baseline value) partial remission: urine protein 0.5-3.5g/24hr (≥ 0.5 g/24hr and \< 3.5 g/24hr), and urine protein decreased by \>50% comparing with the baseline, and serum albumin ≥ 3.0g/dl, and stable renal function (Scr increase ≤ 15% baseline value)
次要结局
- Serum albumin(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Change of SLE-DAI from baseline(at Week 4, 12 and 24)
- CI (Chronic Index)(at Week 24)
- Change of 24-hour urine protein from baseline(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Change of Serum albumin from baseline(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Change of Serum creatinine from baseline(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Percentage of patients converted to other immunosuppressive therapy(during 24 weeks)
- Percentage of patients with dsDNA and ANA converting from positive to negative(during 24 weeks)
- Renal biopsy AI (Active Index)(at Week 24)
- 24-hour urine protein(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- eGFR comparing with baseline(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Percentage of patients with serum creatinine rising to two times of the baseline(during 24 weeks)
- SLE-DAI(at Week 4, 12 and 24)
- Serum creatinine(at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24)
- Immune parameters assessed by ESR, C3, C4 and dsDNA(at Week 4, 12 and 24)
- Change of immune parameters from baseline(at Week 4, 12 and 24)
- Change of Renal biopsy AI (Active Index) from baseline(at Week 24)
- Change of CI (Chronic Index) from baseline(at Week 24)
研究者
研究点 (35)
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