Assess the Efficacy and Safety of Multi-target Therapy in Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of multi-target therapy in the treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ lupus nephritis.

Detailed Description
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To assess the efficacy of FK506 combined with MMF vs intravenous cyclophosphamide (CTX) pulses in treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ Lupus Nephritis (LN). To investigate the safety and tolerability of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ LN.

Official Title
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An Multi-site, Open, Prospective Study to Assess the Efficacy and Safety of Multi-target Therapy in the Treatment of Class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+Ⅴ Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Tacrolimus+Mycophenolate mofetil
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent by subject or guardian 18 to 65 years of age (inclusive 18 and 65), male or female Diagnosis of SLE according to the American College of Rheumatology criteria (1997) Diagnosis of Class Ⅲ,Ⅳ,Ⅴ,Ⅲ+Ⅴand Ⅳ+ⅤLN according to the ISN/RPS 2003 classification by light, immunofluorescence, and electron microscopy within 6 months before enrollment Pathologic chronic index (CI) ≤3' without thrombotic microangiopathy (TMA) SLE Disease Activity Index (DAI) >10' Proteinuria ≥1.5g/d，with or without active urinary sediment Serum creatinine (Scr)≤3.0mg/dl (265.2 mol/L) Exclusion Criteria: Previous treatment with MMF, CTX, tacrolimus, Cyclosporin A (CsA), large doses of immunoglobulin and methylprednisolone (MP), plasmapheresis or renal replacement therapy within the past 12 weeks. Oral glucocorticoids, azathioprine, intravenous MP (≤80mg/d)， short-time CsA (<2 weeks) or leflunomide (<4 weeks) are allowed ALT or AST increase twice above the upper limit of the normal range Hyperglycemia is defined as fasting blood glucose level ≥7.0 mmol/L and/or postprandial blood sugar level>11.1 mmol/L Known hypersensitivity or contraindication to any components of MMF, tacrolimus, CTX or glucocorticoids History of present illness: active HBV infection (HBsAg, HBeAg and anti-HBc positive or HBsAg, anti- HBe and anti-HBc positive), HCV infection, pulmonary tuberculosis, cytomegalovirus(CMV) infection (defined as CMV-IgM positive or CMV-DNA positive), fungal infection or HIV infection, within 3 months before the enrollment non-healed active peptic ulcer within 3 months before the enrollment drug or drinking abuse malnutrition (BMI <18.5kg/m2) or body weight <50Kg Other active diseases, such as: severe cardiovascular diseases chronic obstructive pulmonary disease(COPD)or asthma requiring oral glucocorticoids marrow depression not due to SLE activation: white blood cell count <3000/mm3 or neutrophil count <1300/mm3 or platelet count <50000/mm3 Severe infection or need of antibiotic therapy Female patients who are pregnant/breastfeeding or those patients (both gender) who refused contraception Life-threatening complications such as large hydropericardium, pneumohemorrhagia, lupus encephalopathy and severe pulmonary hypertension or patients in need of MP pulse (>0.5g/d ) treatment because of aggravation of SLE Known to be non-compliance or violation of the protocol base on investigator's judgement Patient who participate of any other investigational drug study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus+Mycophenolate mofetil<br>FK506 4mg/d+MMF 1.0g/d | Drug: Tacrolimus+Mycophenolate mofetil<br>* FK506 4mg/d,MMF 1.0g/d<br>* Other names: FK506+MMF;|
| Active Comparator: Cyclophosphamide<br>CTX iv 0.75 g/m2 body surface area (BSA) | Drug: Cyclophosphamide<br>* CTX 0.75g/m2 BSA<br>* Other names: CTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of FK506 combined with MMF vs intravenous CTX pulses in treatment of class Ⅲ, Ⅳ,Ⅴ, Ⅲ+Ⅴand Ⅳ+Ⅴ LN. | The primary endpoint is the rate of complete remission at 24 weeks. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the other efficacy indicators of FK506 combined with MMF vs intravenous CTX pulses in the treatment of class Ⅲ, Ⅳ,Ⅴ, Ⅲ+Ⅴand Ⅳ+Ⅴ LN. | The secondary endpoints include total remission, time to complete remission and remission, rate of complete remission and remission in patients with different types of LN, changes between baseline and after 24 week of induction treatment in proteinuria, albumin, SCr, eGFR, complement, autoantibodies, SLE-DAI and dosage and concentration of immunosuppressants between groups. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis;multi-target therapy; MMF; FK506