IgA Nephropathy
Conditions
Keywords
IgA nephropathy, mycophenolate mofetil
Brief summary
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
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.
Interventions
DRUGirbesartan
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.
DRUGmethylprednisolone (MP) or prednisone (pred)
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.
DRUGmycophenolate mofetil (MMF)
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Remission of proteinuria (complete or partial) | up to 4.3 years |
Secondary
| Measure | 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） |
Countries
China
Outcome results
None listed