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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT00657059

Collaborator

(none)

151

Enrollment

Location

Arms

140

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
IgA Nephropathy	Drug: irbesartan Drug: methylprednisolone (MP) or prednisone (pred) Drug: mycophenolate mofetil (MMF)	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

151 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2007

Actual Primary Completion Date :

May 1, 2019

Actual Study Completion Date :

May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pred group 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 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. Other Names: Aprovel, Sanofi-synthelabo Drug: methylprednisolone (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.
Active Comparator: MMF Group 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 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. Other Names: Aprovel, Sanofi-synthelabo Drug: mycophenolate 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. Other Names: Cellcept,Roche
Active Comparator: Pred plus MMF Group 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 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. Other Names: Aprovel, Sanofi-synthelabo Drug: methylprednisolone (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. Drug: mycophenolate 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. Other Names: Cellcept,Roche

Arm

Intervention/Treatment

Active Comparator: Pred group

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

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.

Other Names:

Aprovel, Sanofi-synthelabo

Drug: methylprednisolone (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.

Active Comparator: MMF Group

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

Other Names:

Aprovel, Sanofi-synthelabo

Drug: mycophenolate 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.

Other Names:

Cellcept,Roche

Active Comparator: Pred plus MMF Group

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

Other Names:

Aprovel, Sanofi-synthelabo

Drug: methylprednisolone (MP) or prednisone (pred)

Drug: mycophenolate 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.

Other Names:

Cellcept,Roche

Outcome Measures

Primary Outcome Measures

Remission of proteinuria (complete or partial) [up to 4.3 years]

Secondary Outcome Measures

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）]

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The 1st Affiliated Hospital, Sun Yet-sen University	Guangzhou	Guangdong	China	510080

Sponsors and Collaborators

Sun Yat-sen University

Investigators

Principal Investigator: Xueqing Yu, MD, Department of Nephrology, 1st Affiliated Hospital, Sun Yat-Sen University
Principal Investigator: Yunha Liao, MD, Department of Nephrology, 1st Affiliated Hospital of Guangxi Medical University,Guangxi
Principal Investigator: Jinli Zhang, MD, Department of nephrology, People's Hospital of Yunnan Province
Principal Investigator: Junzhou Fu, MD, Department of Nephrology,1st People's Hospital of Guangzhou
Principal Investigator: Anping Xu, MD, Department of Nephrology, 2nd Affiliated Hospital of Sun Yet-Sen University,Guangzhou
Principal Investigator: Zhangsuo liu, MD, Department of Nephrology, 1st Affiliated hospital of Zhengzhou University, Henan
Principal Investigator: Tanqi lou, MD, Department of Nephrology, 3nd affiliated hospital of Sun yatsent university, Guangzhou
Principal Investigator: Li Hao, MD, Department of Nephrology, 2nd Affiliated Hospital of Anhui Medical University, Anhui
Principal Investigator: Menghua Chen, MD, Department of Nephrology, General Hospital of Ningxia Medical University, Ningxia
Principal Investigator: Qinkai Chen, MD, Department of Nephrology, The First Affiliated Hospital of Nanchang University, Jiangxi