Mycophenolate Mofetil Plus Steroid in the Treatment Of Patients With Progressive Idiopathic Membranous Nephropathy (MMF-STOP-IMN)

A Prospective Randomized, Controlled Trial of Mycophenolate Mofetil Plus Steroid in the Treatment Of Patients With Progressive Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) remains a common cause of the nephrotic syndrome in adults. There are few randomized clinical trials regarding the therapeutic effect of mycophenolate mofetil in patients with Idiopathic membranous nephropathy. This study aims to evaluate whether treatment with mycophenolate mofetil is non-inferior to cyclosporins in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Membranous Nephropathy
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Cyclosporins

Detailed Description

Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in adults. In recent year, IMN remains one of the most common glomerular diseases. Long-term remission and stable renal function can prevent idiopathic membranous nephropathy from progressing to end-stage renal disease. Cyclosporine and cyclophosphamide are recommended to be first-line treatment regimen. Corticosteroid is the basic combined drug in the treatment of idiopathic membranous nephropathy. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer renal toxicity than cyclosporin.Besides, high dose prednisone may be effective for patients in Asia according to literatures from Asia. In our study, patients with idiopathic membranous nephropathy would be treated with mycophenolate mofetil and high dose prednisone,whose outcome will be compared with cyclosporin and low dose prednisone. We aims to evaluate whether treatment with mycophenolate mofetil is non-inferior to cyclosporins in inducing long-term remission of proteinuria in patients with idiopathic membranous nephropathy.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangdong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.Patients who provided informed consent
• 2.Patients who are diagnosed as membranous nephropathy by renal biopsy,and other secondary factors are excluded
• 3.18 years of age or older, male or female
• 4.24 hours urine protein or spot urine protein/creatinine ratio > 8.0 g/day at least for twice confirmed

• 5.The patients that satisfy more than three of following items are included even if proteinuria is less than 8 grams per day:

  1. estimated glomerular filtration rate(eGFR) < 60 ml/min/1.73m2
  2. Hypertension (BP above 140/90millimetre of mercury or BP above 120/80millimetre of mercury in patients taking anti-hypertensive agents)
  3. 24 hours urine protein or spot urine protein/creatinine ratio > 5.0 g/day
  4. Serum albumin (g/dL) < 3.0

Exclusion Criteria:

• 1.Severe infective disease
• 2.Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently.
• 3.Clinical history of treatment with other immunosuppressive medication
• 4.Probability of pregnancy, breast feeding woman
• 5.Uncontrolled hypertension (more than 160/100 millimetre of mercury )
• 6.estimated glomerular filtration rate(eGFR)<30 ml/min/1.73m2。
• 7.Abnormal liver function test (more than 3 times above compared with normal value)
• 8.Absolute neutrophil count <1,500/mm3 or leukocyte <2,500/mm3 or platelets <100,000/mm3
• 9.Secondary membranous nephropathy
• 10.Expected life expectancy is less than 1 year
• 11.The researchers evaluated that the patient's compliance was not appropriate for the trial
• 12.Previous or present history of cancer and have risk of recurrence or metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mycophenolate mofetil; Drug: Mycophenolate mofetil, high dose steroid Duration: 1 year	Drug: Mycophenolate Mofetil; steroid 1mg/kg/d and Mycophenolate mofetil 500mg bid
ACTIVE_COMPARATOR: Cyclosporin; Drug: Cyclosporin, low dose steroid Duration: 1 year	Drug: Cyclosporins; steroid 0.15mg/kg/d and Cyclosporin 3-5mg/kg/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission	Urinary protein excretion<0.3 g/d (uPCR<300 mg/g or <30 mg/mmol), confirmed by two values at least 1 week apart, accompanied by a normal serum albumin concentration, and a normal serum creatinine.	after treatment for 1 year.
Partial Remission	Urinary protein excretion <3.5 g/d (uPCR <3500 mg/g or <350 mg/mmol) and a 50% or greater reduction from peak values;confirmed by two values at least 1 week apart, accompanied by an improvement or normalization of the serum albumin concentration and stable serum creatinine.	after treatment for 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
estimated Glomerular Filtration Rate	time to a 50% reduction in baseline estimated Glomerular Filtration Rate (according to CKD-EPI)	after treatment for 1 year
serum creatinine	time to doubling of baseline creatinine	after treatment for 1 year

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: xinling Liang, M.D.,PH.D, Nephrology Dept,Guangdong General Hospital

Publications and helpful links

General Publications

• von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2018
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (ACTUAL): May 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: GGH2016430H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No