A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis

This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.

Inclusion criteria

• 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)

Exclusion criteria

• 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