The Effects of Mycophenolate Mofetil (MMF) on Renal Outcomes in Advanced Immunoglobulin A (IgA) Nephropathy Patients (MAIN)

The Effects of Mycophenolate Mofetil on Renal Outcomes in Patients With Advanced IgA Nephropathy: a Randomized Open-label Study

The study is to evaluate the effect of Mycophenolate Mofetil compared with losartan alone on time to doubling of serum creatinine or the onset of end stage renal disease in patients with advanced IgA nephropathy who are treated with the maximal tolerated daily dose of losartan.The study will also assess the effects of MMF compared with losartan alone on the changes of urine albumin excretion and the changes in estimated glomerular filtration rate.

Study Overview

• Status: Completed
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: Mycophenolate mofetil; Drug: Losartan

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital Southern Medical University
    • Shenzhen, Guangdong, China, 518000
      • The Fourth People's Hospital Shenzhen
    • Zhanjiang, Guangdong, China, 524001
      • The Institute of Nephrology, Guangdong Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy-proven primary IgA nephropathy with urinary proteinuria excretion over 1g/24 hour,subjects must meet 2 of the following criteria:

  1. global glomerular sclerosis plus focal segmental glomerular sclerosis ratio ≥50%
  2. eGFR 30 to 60 ml/min
  3. Hypertension (blood pressure over 140/90 mmHg or taking antihypertensive drugs)

Exclusion Criteria:

1. Secondary IgA nephropathy
2. Familial IgA nephropathy
3. Concomitant disease: cancer, infection, diabetes mellitus, connective tissue disease, abnormal liver function
4. Pregnancy or breasting
5. Inability to comply with study and follow-up procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mycophenolate mofetil; mycophenolate mofetil 1.5g/day and maximum tolerated labeled dose of losartan	Drug: Mycophenolate mofetil; Mycophenolate mofetil 1.5g/day plus maximum tolerated labeled dose losartan
Active Comparator: losartan; maximus tolerated labeled dose of losartan	Drug: Losartan; Maximum tolerated labeled dose of Losartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of mycophenolate mofetil on a composite renal outcomes in subjects with advanced IgA nephropathy	Time to the first occurrence of a component of the composite renal endpoint: Doubling of serum creatinine or the onset of end stage renal disease (ESRD) [needing chronic dialysis or renal transplantation or renal death]	3 years
To evaluate the effects of mycophenolate mofetil on progression of CKD in subjects with advanced IgA nephropathy	A decrease in eGFR of 30% or more and to a level of less than 60 ml/min at the exit visit if the baseline eGFR was 60 ml/min or more. Or a decrease in eGFR of 50% or more at the exit visit if the baseline eGFR was less than 60 ml/min.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of mycophenolate mofetil on the changes of proteinuria in subjects with advanced IgA nephropathy	Changes of urinary protein excretion rate	3 years
To evaluate the effects of mycophenolate mofetil rapid progression of CKD in subjects with advanced IgA nephropathy	Time to 30% reduction in estimated glomerular filtration rate (eGFR); eGFR reduction greater than 5 ml/min/1.73m^2/year	3 years

Collaborators and Investigators

• Sponsor: Fan Fan Hou
• Investigators: Principal Investigator: Fan Fan Hou, M.D., PhD, Division of nephrology, Nanfang Hospital Southern Medical University

Publications and helpful links

General Publications

• Tang SC, Tang AW, Wong SS, Leung JC, Ho YW, Lai KN. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 2010 Mar;77(6):543-9. doi: 10.1038/ki.2009.499. Epub 2009 Dec 23.
• Frisch G, Lin J, Rosenstock J, Markowitz G, D'Agati V, Radhakrishnan J, Preddie D, Crew J, Valeri A, Appel G. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant. 2005 Oct;20(10):2139-45. doi: 10.1093/ndt/gfh974. Epub 2005 Jul 19.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 15, 2013
• First Posted (Estimate): May 16, 2013

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antitubercular Agents; Antibiotics, Antitubercular; Losartan; Mycophenolic Acid
• Other Study ID Numbers: Main