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

Sun Yat-sen University

Status and phase: Completed; Phase 3

Conditions: IgA Nephropathy

Treatments: Drug: methylprednisolone (MP) or prednisone (pred); Drug: irbesartan; Drug: mycophenolate mofetil (MMF)

Study type: Interventional

Funder types: Other

Identifiers

NCT00657059

SYSU-PRGIgAN-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 151 patients

Sex: All

Ages: 14 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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151 participants in 3 patient groups

Pred group

Active Comparator group

Description:

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.

Treatment:

Drug: irbesartan

Drug: methylprednisolone (MP) or prednisone (pred)

MMF Group

Active Comparator group

Description:

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.

Treatment:

Drug: irbesartan

Drug: mycophenolate mofetil (MMF)

Pred plus MMF Group

Active Comparator group

Description:

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.

Treatment:

Drug: irbesartan

Drug: mycophenolate mofetil (MMF)

Drug: methylprednisolone (MP) or prednisone (pred)