Mycophenolate Mofetil Plus Steroid in the Treatment Of Patients With Progressive Idiopathic Membranous Nephropathy

Study Overview
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Brief Summary
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Idiopathic membranous nephropathy (IMN) remains a common cause of the nephrotic syndrome in adults. There are few randomized clinical trials regarding the therapeutic effect of mycophenolate mofetil in patients with Idiopathic membranous nephropathy. This study aims to evaluate whether treatment with mycophenolate mofetil is non-inferior to cyclosporins in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

Detailed Description
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Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in adults. In recent year, IMN remains one of the most common glomerular diseases. Long-term remission and stable renal function can prevent idiopathic membranous nephropathy from progressing to end-stage renal disease. Cyclosporine and cyclophosphamide are recommended to be first-line treatment regimen. Corticosteroid is the basic combined drug in the treatment of idiopathic membranous nephropathy. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer renal toxicity than cyclosporin.Besides, high dose prednisone may be effective for patients in Asia according to literatures from Asia. In our study, patients with idiopathic membranous nephropathy would be treated with mycophenolate mofetil and high dose prednisone,whose outcome will be compared with cyclosporin and low dose prednisone. We aims to evaluate whether treatment with mycophenolate mofetil is non-inferior to cyclosporins in inducing long-term remission of proteinuria in patients with idiopathic membranous nephropathy.

Official Title
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A Prospective Randomized, Controlled Trial of Mycophenolate Mofetil Plus Steroid in the Treatment Of Patients With Progressive Idiopathic Membranous Nephropathy

Conditions
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Idiopathic Membranous Nephropathy

Intervention / Treatment
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* Drug: Mycophenolate Mofetil
* Drug: Cyclosporins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Patients who provided informed consent 2.Patients who are diagnosed as membranous nephropathy by renal biopsy,and other secondary factors are excluded 3.18 years of age or older, male or female 4.24 hours urine protein or spot urine protein/creatinine ratio > 8.0 g/day at least for twice confirmed 5.The patients that satisfy more than three of following items are included even if proteinuria is less than 8 grams per day: estimated glomerular filtration rate(eGFR) < 60 ml/min/1.73m2 Hypertension (BP above 140/90millimetre of mercury or BP above 120/80millimetre of mercury 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 Exclusion Criteria: 1.Severe infective disease 2.Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently. 3.Clinical history of treatment with other immunosuppressive medication 4.Probability of pregnancy, breast feeding woman 5.Uncontrolled hypertension (more than 160/100 millimetre of mercury ) 6.estimated glomerular filtration rate(eGFR)<30 ml/min/1.73m2。 7.Abnormal liver function test (more than 3 times above compared with normal value) 8.Absolute neutrophil count <1,500/mm3 or leukocyte <2,500/mm3 or platelets <100,000/mm3 9.Secondary membranous nephropathy 10.Expected life expectancy is less than 1 year 11.The researchers evaluated that the patient's compliance was not appropriate for the trial 12.Previous or present history of cancer and have risk of recurrence or metastasis

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: Parallel Assignment
Interventional Model Description: Drug: Mycophenolate mofetil, high dose steroid Drug: Cyclosporin, low dose steroid
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mycophenolate mofetil<br>Drug: Mycophenolate mofetil, high dose steroid Duration: 1 year | Drug: Mycophenolate Mofetil<br>* steroid 1mg/kg/d and Mycophenolate mofetil 500mg bid<br>|
| Active Comparator: Cyclosporin<br>Drug: Cyclosporin, low dose steroid Duration: 1 year | Drug: Cyclosporins<br>* steroid 0.15mg/kg/d and Cyclosporin 3-5mg/kg/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission | Urinary protein excretion<0.3 g/d (uPCR<300 mg/g or <30 mg/mmol), confirmed by two values at least 1 week apart, accompanied by a normal serum albumin concentration, and a normal serum creatinine. | after treatment for 1 year. | 
| Partial Remission | Urinary protein excretion <3.5 g/d (uPCR <3500 mg/g or <350 mg/mmol) and a 50% or greater reduction from peak values;confirmed by two values at least 1 week apart, accompanied by an improvement or normalization of the serum albumin concentration and stable serum creatinine. | after treatment for 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| estimated Glomerular Filtration Rate | time to a 50% reduction in baseline estimated Glomerular Filtration Rate (according to CKD-EPI) | after treatment for 1 year | 
| serum creatinine | time to doubling of baseline creatinine | after treatment for 1 year |