The Effects of Mycophenolate Mofetil (MMF) on Renal Outcomes in Advanced Immunoglobulin A (IgA) Nephropathy Patients

Study Overview
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Brief Summary
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The study is to evaluate the effect of Mycophenolate Mofetil compared with losartan alone on time to doubling of serum creatinine or the onset of end stage renal disease in patients with advanced IgA nephropathy who are treated with the maximal tolerated daily dose of losartan.The study will also assess the effects of MMF compared with losartan alone on the changes of urine albumin excretion and the changes in estimated glomerular filtration rate.

Official Title
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The Effects of Mycophenolate Mofetil on Renal Outcomes in Patients With Advanced IgA Nephropathy: a Randomized Open-label Study

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: Mycophenolate mofetil
* Drug: Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven primary IgA nephropathy with urinary proteinuria excretion over 1g/24 hour,subjects must meet 2 of the following criteria: global glomerular sclerosis plus focal segmental glomerular sclerosis ratio ≥50% eGFR 30 to 60 ml/min Hypertension (blood pressure over 140/90 mmHg or taking antihypertensive drugs) Exclusion Criteria: Secondary IgA nephropathy Familial IgA nephropathy Concomitant disease: cancer, infection, diabetes mellitus, connective tissue disease, abnormal liver function Pregnancy or breasting Inability to comply with study and follow-up procedures

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 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: mycophenolate mofetil<br>mycophenolate mofetil 1.5g/day and maximum tolerated labeled dose of losartan | Drug: Mycophenolate mofetil<br>* Mycophenolate mofetil 1.5g/day plus maximum tolerated labeled dose losartan<br>|
| Active Comparator: losartan<br>maximus tolerated labeled dose of losartan | Drug: Losartan<br>* Maximum tolerated labeled dose of Losartan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of mycophenolate mofetil on a composite renal outcomes in subjects with advanced IgA nephropathy | Time to the first occurrence of a component of the composite renal endpoint: Doubling of serum creatinine or the onset of end stage renal disease (ESRD) [needing chronic dialysis or renal transplantation or renal death] | 3 years | 
| To evaluate the effects of mycophenolate mofetil on progression of CKD in subjects with advanced IgA nephropathy | A decrease in eGFR of 30% or more and to a level of less than 60 ml/min at the exit visit if the baseline eGFR was 60 ml/min or more. Or a decrease in eGFR of 50% or more at the exit visit if the baseline eGFR was less than 60 ml/min. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of mycophenolate mofetil on the changes of proteinuria in subjects with advanced IgA nephropathy | Changes of urinary protein excretion rate | 3 years | 
| To evaluate the effects of mycophenolate mofetil rapid progression of CKD in subjects with advanced IgA nephropathy | Time to 30% reduction in estimated glomerular filtration rate (eGFR); eGFR reduction greater than 5 ml/min/1.73m^2/year | 3 years |