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

NCT00657059 | Completed Phase 3 DMC

• 1 other identifier: SYSU-PRGIgAN-001
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

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.

Conditions

IgA Nephropathy

Keywords

IgA nephropathy; mycophenolate mofetil

Outcome Measures

Primary Outcomes (1)

• Remission of proteinuria (complete or partial)

  up to 4.3 years

Secondary Outcomes (1)

• 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）

Study Arms (3)

Pred group

ACTIVE COMPARATOR

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; Drug: methylprednisolone (MP) or prednisone (pred)

MMF Group

ACTIVE COMPARATOR

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; Drug: mycophenolate mofetil (MMF)

Pred plus MMF Group

ACTIVE COMPARATOR

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

Interventions

irbesartan 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.

Also known as: Aprovel, Sanofi-synthelabo

MMF Group; Pred group; Pred plus MMF Group

methylprednisolone (MP) or prednisone (pred) 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.

Pred group; Pred plus MMF Group

mycophenolate mofetil (MMF) 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.

Also known as: Cellcept,Roche

MMF Group; Pred plus MMF Group

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The 1st Affiliated Hospital, Sun Yet-sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• 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.

  PMID: 38864363 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

Irbesartan; Methylprednisolone; Prednisone; prednylidene; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: September 1, 2007
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: December 3, 2019

Record last verified: 2019-12

Locations

CN (1)