The Efficacy of Enteric-coated Mycophenolate Sodium (EC-MPS) (Myfortic) in The Treatment of Relapse or Resistant Proliferative Lupus Nephritis

Study Overview
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Brief Summary
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To investigate the efficacy and safety of enteric-coated mycophenolate sodium (Myfortic) as compared to intravenous cyclophosphamide in the treatment of active nephritis. The primary outcomes are complete and partial renal remission, as assessed by renal function, urinary sediment and proteinuria in patients with International Society of Nephrology/ Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis.

Detailed Description
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In this study, there are two sub-studies in order to define secondary endpoints. Pharmacokinetics study of Mycophenolic acid Identify biomarkers for therapy-resistant prediction. Identify biomarkers for predicting a loss of kidney function.

Official Title
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The Clinical Efficacy and Economic Evaluation of EC-MPS (Myfortic) in the Treatment of Relapse or Resistant Proliferative Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: mycophenolate sodium
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 16 years of above at the time of screening ability and willingness to provide written informed consent (or to obtain consent from parent guardian where applicable) and to comply with the schedule of protocol requirements Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE. The 4 criteria do not have to be present at the time of screening Active lupus nephritis defined as follows: Biopsy proven (within 16 weeks prior to screening) ISN Class III or IV (A or A/C) not include III(C) IV(C) and VI (>90% chronic irreversible scarring) Relapse or resistant to (3 consecutive doses) IVCY Resistant lupus or Relapse lupus nephritis defined as follows: Increase in serum creatinine >/= 0.3 mg/dl or Increase in proteinuria > 1.5 g/day (which must have improved by ≥ 50% in the preceding 3 months) Life-time cumulative dose of IVCY > 6 grams Female patients of childbearing potential must have a negative serum pregnancy Exclusion Criteria: Relates to SLE Diagnosis of rapid progressive glomerulonephritis (RPGN): doubling serum creatinine and/or crescentic glomeruli ≥ 30% Severe renal impairment as defined by calculated creatinine clearance or MDRD-GFR < 30 ml/min(except creatinine clearance or MDRD-GFR > 50 ml/min in the 12 weeks prior to screening) History of serious disease or complication in any organ system that not appropriate to treatment immunosuppressive drug groups. Severe extra-renal organ involvement Related to Treatment Previous of any Mycophenolate groups in the 6 months prior to screening Treatment with any investigational drugs in the 3 months prior to screening Related to General Health Pregnancy or breast feeding mothers. Concomitant condition which has required treatment moderate to high dose steroid in the 12 weeks prior to screening. Evidence of significant uncontrolled concomitant disease in any organ system not related to SLE. History of cancer, including solid tumors, hematological malignancies and carcinoma. Evidence of current abuse of drugs or alcohol. Related to Laboratory Findings Neutrophile < 1,500/mm3, Hb < 7g/L, Platelet < 50,000/mm3 (except active SLE) Positive HBsAg or anti-HCV or anti-HIV.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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>Oral mycophenolate sodium 1440 mg per day for 12 months | Drug: mycophenolate sodium<br>* per oral, twice daily, for 12 months<br>* Other names: Myfortic;|
| Active Comparator: 2<br>Intravenous cyclophosphamide monthly for 6 months | Drug: cyclophosphamide<br>* intravenous, monthly, for 6 months<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of enteric-coated Mycophenolate Sodium at 12 months in the treatment of lupus nephritis |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cost-effectiveness of using enteric-coated Mycophenolate Sodium as compared to standard treatment |  | 12 months | 
| The ratio of patients with declined renal function |  | 12 months | 
| Time to remission |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis, mycophenolate sodium, cyclophosphamide