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

NCT ID: NCT00843856

Last Updated: 2019-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-03
• Study Completion Date: 2018-09-18

Brief Summary

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.

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.

Conditions

Glomerulonephritis, Membranous

Keywords

Glomerulonephritis

Study Design

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

Study Groups

tacrolimus

Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L

Group Type: ACTIVE_COMPARATOR

tacrolimus

Intervention Type: DRUG

tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml

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

Group Type: ACTIVE_COMPARATOR

tacrolimus and mycophenolate mofetil

Intervention Type: DRUG

tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L

Interventions

tacrolimus

tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

prograff; prograf; cellcept

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imperial College Healthcare NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Megan Griffith, MBChB PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Hammersmith Hospital

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 31492152 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34778952 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2008-001009-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13HH1282

Identifier Type: -

Identifier Source: org_study_id