Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy

Study Overview
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Brief Summary
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Cyclosporin decreases proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a risk of side effects such as nephrotoxicity. The investigators plan to the study to evaluate whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effect.

Detailed Description
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Idiopathic membranous nephropathy is most common cause of glomerulonephritis in adults. Persistent high grade proteinuria or progressively decrease of renal function is a risk factor for end stage renal disease in idiopathic membranous nephropathy. It has been reported that cyclosporin in patients with idiopathic membranous nephropathy decreases proteinuria and improve renal function. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer side effect than cyclosporin. In this study patients with high risk group of progressive idiopathic membranous nephropathy will be treated with mycophenolate mofetil and low dose prednisone. The outcome will be compared to controls treated with cyclosporin and low dose prednisone.

Official Title
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A Randomized Controlled Multi-center Trial of Mycophenolate Mofetil for the Patient With High Risk Membranous Nephropathy

Conditions
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Glomerulonephritis, Membranous

Intervention / Treatment
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* Drug: Mycophenolate mofetil, low dose steroid
* Drug: Cyclosporin, low dose steroid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with idiopathic membranous nephropathy The duration of disease is less than twelve months Patients with persistent proteinuria more than 8 grams per day Patients who provided informed consent The cases that satisfy more than three of following items even if proteinuria is less than 8 grams per day: eGFR < 60 ml/min/1.73m2 Hypertension (BP above 140/90mmHg or BP above 120/80 in patients taking anti-hypertensive agents) 24 hours urine protein or spot urine protein/creatinine ratio > 5.0 g/day Serum albumin (g/dL) < 3.0 Selectivity index > 0.2 Exclusion Criteria: Severe digestive organ disease Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently. Clinical history of treatment with other immunosuppressive medication Probability of pregnancy, breast feeding woman Uncontrolled hypertension (more than 160/100mmHg) Uncontrolled systemic disease Drug addiction or alcoholics within 6 months eGFR is less than 30ml/min at screening Abnormal liver function test (more than 3 times above compared with normal value) Absolute neutrophil count <1,500/mm3 or leukocyte <2,500/mm3 or platelets <100,000/mm3 Secondary membranous nephropathy Expected life expectancy is less than 1 year

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mycophenolate mofetil, low dose steroid<br> | Drug: Mycophenolate mofetil, low dose steroid<br>* Mycophenolate Mofetil: Myconol capsule 250mg, Myconol 500 mg bid per day (less than 50kg), 750   1000 mg bid per day (more than 50kg) Steroid: Methylprednisone 4mg tablet or Prednisolone 5mg tablet or Deflazacort 6mg tablet. Prednisolone dose: 0.15mg/kg up to a maximum dose of 15mg/day Duration: 48 weeks<br>* Other names: Myconol, MMF;|
| Active Comparator: Cyclosporin, low dose steroid<br> | Drug: Cyclosporin, low dose steroid<br>* Cyclosporin: Implanta soft cap (cyclosporin microemulsion) 25mg/100mg, starting dose of 4mg/kg per day and titrate according to investigator's decision based on cyclosporin trough level (100±50 ng/ml) Steroid: same dosage with active comparator goup Duration: 48 weeks<br>* Other names: Implanta soft capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of complete remission | Complete remission: Reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL | at 48 week after treatment | 
| Percentage of partial remission | Partial remission: Reduction in proteinuria to greater than 50 percent of initial values or absolute values of proteinuria between 200 mg and 3.5 g per day | at 48 week after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| estimated Glomerular filtration rate (eGFR) | The change of eGFR mesured by Modification of Diet in Renal Disease (MDRD) study equation from baseline to 1 year after treatment | at 48 week after treatment | 
| Relapse | A relapse is return of proteinuria to approximately 3.5g/day in patients who had previously undergone a complete or partial remission | For 48 weeks after treatment | 
| Proteinuria | The change of proteinuria from baseline to 48 week after treatment | at 48 week after treatment | 
| Side effects | Any undesired effects of interventional drugs | For 48 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic membranous nephropathy, Mycophenolate mofetil, Proteinuria, Renal function