Efficacy and Safety of Tacrolimus Sustained-release Capsules in Induction Treatment in Refractory Lupus Nephritis

Study Overview
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Brief Summary
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This a pilot study to evaluate the efficacy and safety of Tacrolimus Sustained-release Capsules (ADVAGRAF) treatment for the induction therapy of refractory lupus nephritis (LN).

Conditions
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Nephritis, Lupus

Intervention / Treatment
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* Drug: Tacrolimus Sustained-release Capsules (ADVAGRAF)


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 study with a histologic diagnosis (ISN/RPS 2003 classification of LN) class IV, V, V+ III, V+ IV; Usage of intravenous pulse cyclophosphamide for more than 3 times or immunosuppression therapy (AZA, MMF, oral cyclophosphamide, ect) for more than 6 months; proteinuria > 1g/24hr or Scr > 1.3 mg/dl or active urinary sediment (erythrocyte cast, > 5 WBC/high power field (hpf) (excluding infection), > 5 RBC/hpf); Provision of written informed consent by subject or guardian Exclusion Criteria: Inability or unwillingness to provide written informed consent ; Usage of immunosuppression therapy (MMF, CTX, CysA, MTX etc) for more than 1 week within 1 month or intravenous MP Pulse treatment prior to entry; Scr > 4mg/dl (354umol/L); Needing pulse intravenous MP or intravenous immunoglobulin; Lupus encephalopathy; Diagnosed DM; Malignant tumors (except fully cured basal cell carcinoma); History of significant gastrointestinal disorders (e.g. active peptic ulcer disease or pancreatitis) within 3 month prior to enter this study; Known hypersensitivity or contraindication to tacrolimus, corticosteroids Any Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C; Participation in another clinic trial and/or receipt of investigational drugs within 4 weeks prior to screening; Pregnancy, nursing or use of a non-reliable method of contraception.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADVAGRAF<br>Tacrolimus Sustained-release Capsules (ADVAGRAF) treatment in induction phase | Drug: Tacrolimus Sustained-release Capsules (ADVAGRAF)<br>* Started: 0.05-0.1mg/kg/d, one time per day, the blood level 5-10ng/ml in the induction treatment.<br>* Other names: ADVAGRAF: Tacrolimus Sustained-release Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate (complete or partial remission) |  | 6 months after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of proteinuria |  | every 3 months up to 6 months | 
| SLEDAI scores | SLEDAI:Systemic Lupus Erythematosus Disease Activity Index (Bombardier et al, 1992). | every 3 months up to 6 months | 
| Number of participants with adverse events as a measure of safety and tolerability | Adverse events, including infections, transient increases in serum creatinine, gastrointestinal complaints, liver function disorder and glucose intolerance, etc. | every 3 months up to 6 months | 
| The changes of renal function |  | every 3 months up to 6 months | 
| Relapse |  | every 3 months up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephritis, Lupus, Tacrolimus