Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis (MTAC)

Mycophenolate Mofetil and Tacrolimus vs Tacrolimus Alone for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG)

Study Hypothesis: When mycophenolate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy.

Study Overview

• Status: Completed
• Conditions: Glomerulonephritis, Membranous
• Intervention / Treatment: Drug: tacrolimus; Drug: tacrolimus and mycophenolate mofetil

Detailed Description

Membranous nephropathy is a common cause of nephrotic syndrome in adults. It is difficult to treat and if persistent leads to end stage renal failure in a significant number of patients. It is currently treated in this institution with tacrolimus monotherapy. This is effective in the majority of patients in reducing proteinuria but the remissions are often partial and patients tend to relapse when the tacrolimus treatment is stopped. We propose to use mycophenolate mofetil in combination with tacrolimus with the aim of obtaining a more complete initial response to treatment, a decreased rate of relapse on withdrawal of therapy and less progression of renal failure. This will be a randomised control trial, patients will be randomised to receive treatment with tacrolimus alone (our current standard therapy)or treatment with tacrolimus and mycophenolate mofetil. Participants will receive treatment for up to 2 years and then be monitored for relapse of their nephrotic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 OHS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic membranous glomerulonephritis on renal biopsy
• Proteinuria - protein/creatinine ratio (PCR) > 100 units with hypoalbuminaemia or PCR > 300 units with normal serum albumin despite 3 months treatment with maximum tolerated doses of ace inhibitors and angiotensin 2 antagonists (or shorter if life threatening complications of nephrotic syndrome require institution of immediate immunosuppression)
• Male or female patients aged 18 to 80 years

Exclusion Criteria:

• Hepatitis B hepatitis C or HIV positive
• Malignancy (all patients must have a CT chest abdomen and pelvis and other investigations if clinically indicated)
• Untreated infection
• Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception
• Any condition judged by the investigator that would cause the study to be detrimental to the patient

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
Active Comparator: tacrolimus; Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L	Drug: tacrolimus; tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml; Other Names: prograff
Active Comparator: tacrolimus and mycophenolate mofetil; tacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenolate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L	Drug: tacrolimus and mycophenolate mofetil; tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L; Other Names: prograf; cellcept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patient Who Gained Remission From the Nephrotic Syndrome	Efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy.	10-109 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Achieved Remission	The degree of remission of proteinuria obtained (complete or partial) The rate of decline of renal function measured by the Modification of Diet in Renal Disease equation for glomerular filtration rate.	6-12 months

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: Megan Griffith, MBChB PhD, Imperial College London

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.
• Nikolopoulou A, Condon M, Turner-Stokes T, Cook HT, Duncan N, Galliford JW, Levy JB, Lightstone L, Pusey CD, Roufosse C, Cairns TD, Griffith ME. Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. BMC Nephrol. 2019 Sep 6;20(1):352. doi: 10.1186/s12882-019-1539-z.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2009
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): September 18, 2018

Study Registration Dates

• First Submitted: February 12, 2009
• First Submitted That Met QC Criteria: February 12, 2009
• First Posted (Estimate): February 13, 2009

Study Record Updates

• Last Update Posted (Actual): December 12, 2019
• Last Update Submitted That Met QC Criteria: November 21, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Glomerulonephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulonephritis, Membranous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: 13HH1282; 2008-001009-41 (EudraCT Number)

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