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

NCT ID: NCT00657059

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2019-05-31

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.

Conditions

IgA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

irbesartan

Intervention Type: DRUG

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.

methylprednisolone (MP) or prednisone (pred)

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

irbesartan

Intervention Type: DRUG

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.

mycophenolate mofetil (MMF)

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

irbesartan

Intervention Type: DRUG

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.

methylprednisolone (MP) or prednisone (pred)

Intervention Type: DRUG

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.

mycophenolate mofetil (MMF)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Aprovel, Sanofi-synthelabo; Cellcept,Roche

Eligibility Criteria

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

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Xue Qing Yu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xueqing Yu, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 1st Affiliated Hospital, Sun Yat-Sen University

Yunha Liao, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 1st Affiliated Hospital of Guangxi Medical University,Guangxi

Jinli Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of nephrology, People's Hospital of Yunnan Province

Junzhou Fu, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology,1st People's Hospital of Guangzhou

Anping Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 2nd Affiliated Hospital of Sun Yet-Sen University,Guangzhou

Zhangsuo liu, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 1st Affiliated hospital of Zhengzhou University, Henan

Tanqi lou, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 3nd affiliated hospital of Sun yatsent university, Guangzhou

Li Hao, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, 2nd Affiliated Hospital of Anhui Medical University, Anhui

Menghua Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, General Hospital of Ningxia Medical University, Ningxia

Qinkai Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, The First Affiliated Hospital of Nanchang University, Jiangxi

Locations

The 1st Affiliated Hospital, Sun Yet-sen University

Guangzhou, Guangdong, China

Countries

China

References

Alladin A, Hahn D, Hodson EM, Ravani P, Pfister K, Quinn RR, Samuel SM. Immunosuppressive therapy for IgA nephropathy in children. Cochrane Database Syst Rev. 2024 Jun 12;6(6):CD015060. doi: 10.1002/14651858.CD015060.pub2.

Reference Type: DERIVED

PMID: 38864363 (View on PubMed)

Other Identifiers

SYSU-PRGIgAN-001

Identifier Type: -

Identifier Source: org_study_id