Prospective, Randomized, Multicenter, Control Study to Assess the Efficacy and Safety of Tacrolimus in Induction and Maintenance Phase Treatment in Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of tacrolimus vs intravenous cyclophosphamide pulses treatment for the induction therapy of LN(III,IV,V). To compare the efficacy and safety of tacrolimus vs Azathioprine for the maintenance therapy of LN(III,IV,V).

Conditions
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Kidney Diseases, Lupus Nephritis, Tacrolimus, Induction Phase, Maintenance Phase

Intervention / Treatment
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* Drug: tacrolimus (FK506)
* Drug: cyclophosphamide or azathioprine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of either sex, 14-65 years of age; Diagnosis of SLE according to the ACR criteria(1997); Kidney biopsy within the 6 months prior to first randomization with a histologic diagnosis (ISN/RPS 2003 classification of LN) class III, IV, V; Class IV LN: proteinuria >1g/24hr or Scr>115umol/L; Class III or V LN: proteinuria >2g/24hr or Scr>115umol/L; Provision of written informed consent by subject or guardian. Exclusion Criteria: Inability or unwillingness to provide written informed consent ; Known hypersensitivity or contraindication to tacrolimus, cyclophosphamide , azathioprine, corticosteroids; Usage of immunosuppression therapy (MMF, CTX, CysA, MTX ect) for more than 1 week within 1 month prior to first randomization; Pregnancy, nursing or use of a non-reliable method of contraception; Continuous dialysis starting more than 2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration of more than 8 weeks; Previous kidney transplant or planted transplant; Scr > 4mg/dl (353umol/L); Active hepatitis, with liver dysfunction; Diagnosed DM; Participation in another clinic trial and/or receipt of investigational drugs within 4 weeks prior to screening .

Ages Eligible for Study
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Minimum Age: 14 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: 1<br>tacrolimus(fk506) treatment in induction and maintenance phase | Drug: tacrolimus (FK506)<br>* Started: 0.05-0.1mg/kg/d,divided into two daily dose at 12hr; the blood level:5-10ng/ml in induction phase;and 4-6ng/ml in maintenance phase;<br>|
| Active Comparator: 2<br>intravenous cyclophosphamide pulses treatment in induction phase; and Aza in the maintenance phase | Drug: cyclophosphamide or azathioprine<br>* Induction phase: CTX 0.75g/m2 monthly Maintenance phase: AZA 2mg/kg/d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate |  | 2006-2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function, proteinuria, relapse. |  | 2006-2008 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tacrolimus, lupus nephritis