A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT02457221
- Lead Sponsor
- Astellas Pharma China, Inc.
- Brief Summary
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.
- Detailed Description
This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 314
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cyclophosphamide group Cyclophosphamide injections Cyclophosphamide injections + steroid Cyclophosphamide group Prednisone Cyclophosphamide injections + steroid Tacrolimus group Tacrolimus capsules Tacrolimus capsules + steroid Tacrolimus group Prednisone Tacrolimus capsules + steroid
- Primary Outcome Measures
Name Time Method Remission rate (complete remission + partial remission) 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)
- Secondary Outcome Measures
Name Time Method Change of SLE-DAI from baseline at Week 4, 12 and 24 Serum albumin at Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 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 ANA: Antinuclear Antibody
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 eGFR: Estimated Glomerular Filtration Rate
Percentage of patients with serum creatinine rising to two times of the baseline during 24 weeks SLE-DAI at Week 4, 12 and 24 SLE-DAI: Systemic Lupus Erythematosus - Disease Activity Index
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 ESR: Erythrocyte Sedimentation Rate, C3, C4: Complement C3, C4, dsDNA: Anti-Double-Stranded DNA Antibodies
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
Trial Locations
- Locations (35)
Site CN00005
🇨🇳Dalian, Liaoning, China
Site CN00045
🇨🇳Liuzhou, Guangxi, China
Site CN00025
🇨🇳Nanjing, Jiangsu, China
Site CN00030
🇨🇳Beijing, Beijing, China
Site CN00056
🇨🇳Guangzhou, Guangdong, China
Site CN00017
🇨🇳Shenzhen, Guangdong, China
Site CN00023
🇨🇳Wuhan, Hubei, China
Site CN00012
🇨🇳Nanjing, Jiangsu, China
Site CN00015
🇨🇳Shanghai, Shanghai, China
Site CN00002
🇨🇳Chengdu, Sichuan, China
Site CN00010
🇨🇳Hangzhou, Zhejiang, China
Site CN00043
🇨🇳Hefei, Anhui, China
Site CN00041
🇨🇳Xiamen, Fujian, China
Site CN00034
🇨🇳Beijing, Beijing, China
Site CN00037
🇨🇳Nanning, Guangxi, China
Site CN00038
🇨🇳Nanning, Guangxi, China
Site CN00020
🇨🇳Shijiazhuang, Hebei, China
Site CN00049
🇨🇳Wuxi, Jiangsu, China
Site CN00024
🇨🇳Wuhan, Hubei, China
Site CN00047
🇨🇳Shijiazhuang, Hebei, China
Site CN00028
🇨🇳Zhengzhou, Henan, China
Site CN00027
🇨🇳Changsha, Hunan, China
Site CN00032
🇨🇳Qingdao, Shandong, China
Site CN00052
🇨🇳Taiyuan, Shanxi, China
Site CN00019
🇨🇳Shenyang, Liaoning, China
Site CN00001
🇨🇳Shanghai, Shanghai, China
Site CN00014
🇨🇳Shanghai, Shanghai, China
Site CN00050
🇨🇳Changsha, Hunan, China
Site CN00013
🇨🇳Nanjing, Jiangsu, China
Site CN00026
🇨🇳Changchun, Jilin, China
Site CN00042
🇨🇳Changchun, Jilin, China
Site CN00018
🇨🇳Shenyang, Liaoning, China
Site CN00003
🇨🇳Chengdu, Sichuan, China
Site CN00021
🇨🇳Tianjin, Tianjin, China
Site CN00044
🇨🇳Wulumuqi, Xinjiang, China