Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN)

Study Overview
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Brief Summary
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A multi-center, randomized, controlled clinical trial to evaluate the short-term and long-term efficacy and safety of mycophenolate mofetil (MMF) in reducing proteinuria and preserving renal function in patients with IgAN who have pre-treated (and continue to be treated) with angiotensin II receptor blockers (ARB), compared to the corticosteroids.

Detailed Description
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There are four phases of study for each subject. Phase 1 the screening phase. During this phase each potential subject will be evaluated to determine if he/she is eligible for the study. Phase 2 the ARB lead-in phase will last for three months. Phase 3 the intervention phase. Each subject will be randomly received 12 months treatment with the study drugs (MMF, prednisone or MMF plus prednisone) Phase 4 following-up phase. All the patients will be followed by 3 years after study drug stopped.

Official Title
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A Prospective, Multicenter, Randomized Controlled Trial of Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN)

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: irbesartan
* Drug: methylprednisolone (MP) or prednisone (pred)
* Drug: mycophenolate mofetil (MMF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness to sign an informed consent Age:14 60 years, regardless of gender Clinical evaluation and renal biopsy diagnostic for IgAN, excluded secondary IgAN. Renal histological criteria should be defined by Lee's glomerular grading system. 1 g/day <= proteinuria < 3.5 g/day, or UPr/Cr ratio ≥ 0.6 (male) or ≥ 0.8 (female) when taking ARB eGFR ≥ 40 mL/min/1.73 m2 Exclusion Criteria: Inability or unwillingness to sign the informed consent Inability or unwillingness to meet the scheme demands raised by the investigators Rapidly progressive nephritic syndrome and acute renal failure, including rapidly progressive IgAN ( IgAN with rapid decline in renal function characterized histologically by necrotizing vasculitis and crescent formation≥30%) necessitating the use of other immunosuppressive agents. Secondary IgAN such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B -associated nephritis est GFR < 40 mL/min/1.73m2 Malignant hypertension that is difficult to be controlled by oral drugs Cirrhosis, chronic active liver disease. History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease.) Any Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C. Other major organ system disease (e.g. serious cardiovascular diseases including congestive heart failure , chronic obstructive pulmonary disease, asthma requiring oral steroid treatment or central nervous system diseases) Malignant tumors (except fully cured basal cell carcinoma) Absolute neutrophil count < 1500／mm3, absolute platelet count <75000／mm3 or hematocrit (Hct) <28% (anemic subjects may be reevaluated after the anemia has been treated.) Known allergy, contraindication or intolerance to the MMF, corticosteroids or ACEI/ARB. Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception Current exposure to MMF or azathioprine. In case of current treatment with oral steroid or ACEI/ARB, entry is permitted after corticosteroids or ACEI/ARB are stopped for 2 weeks. Current or recent (within 30 days) exposure to any other investigational drugs

Ages Eligible for Study
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Minimum Age: 14 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 |
| --- | --- |
| Active Comparator: Pred group<br>Pred Group: Prednisone treatment Patients will give methylprednisolone intravenously at a dose of 0.5 g/day for 3 days at the start of months 1, 3, and 5; then take oral prednisone (0.5 mg/kg/d) on alternate days. Prednison will be tapered 5 mg per month from the seventh month to the 12th month. | Drug: irbesartan<br>* In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg   300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase.<br>* Other names: Aprovel, Sanofi-synthelabo;Drug: methylprednisolone (MP) or prednisone (pred)<br>* Patients will take oral Pred ( 0.5 mg/kg/d) on alternate days, and on the first, third and fifth months of the drug treatment phase, patients will be given intravenous pulse therapy with methylprednisolone ( 0.5 g/day) for 3 successive days. And after 6 months, Pred should be tapered to be stopped until the end of the 12-month course of treatment.<br>|
| Active Comparator: MMF Group<br>MMF Group: MMF treatment Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt < 50kg) for the first 6-month of drug treatment phase, then 0.5 bid for the remaining 6-month. | Drug: irbesartan<br>* In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg   300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase.<br>* Other names: Aprovel, Sanofi-synthelabo;Drug: mycophenolate mofetil (MMF)<br>* Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt < 50kg) for the first 6-month of drug treatment phase, then to 0.5 bid (wt ≥ 50kg) for the remaining 6-month.<br>* Other names: Cellcept,Roche;|
| Active Comparator: Pred plus MMF Group<br>Pred plus MMF Group: Prednisone plus MMF treatment. Patients will give methylprednisolone intravenously at a dose of 0.5 g/day for 3 days at the start of months 1, 3, and 5; then take oral prednisone (0.5 mg/kg/d) on alternate days. Prednison will be tapered 5 mg per month from the seventh month to the 12th month. Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt < 50kg) for the first 6-month of drug treatment phase, then 0.5 bid for the remaining 6-month. | Drug: irbesartan<br>* In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg   300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase.<br>* Other names: Aprovel, Sanofi-synthelabo;Drug: methylprednisolone (MP) or prednisone (pred)<br>* Patients will take oral Pred ( 0.5 mg/kg/d) on alternate days, and on the first, third and fifth months of the drug treatment phase, patients will be given intravenous pulse therapy with methylprednisolone ( 0.5 g/day) for 3 successive days. And after 6 months, Pred should be tapered to be stopped until the end of the 12-month course of treatment.<br>Drug: mycophenolate mofetil (MMF)<br>* Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt < 50kg) for the first 6-month of drug treatment phase, then to 0.5 bid (wt ≥ 50kg) for the remaining 6-month.<br>* Other names: Cellcept,Roche;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission of proteinuria (complete or partial) |  | up to 4.3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine (SCr) levels, or a 25% decline from baseline eGFR levels, or onset of end-stage renal disease or dialysis treatment, or kidney transplantation) |  | every 6 month for 4.3 years（including 3 months ARB leading-in phase， 1 years' treatment phase and 3 years' follow-up） | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA nephropathy, mycophenolate mofetil