Clinical trial NCT00843856: Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis
Official title: Mycophenolate Mofetil and Tacrolimus vs Tacrolimus Alone for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Glomerulonephritis, Membranous
Keywords: Glomerulonephritis
Lead sponsor: Imperial College Healthcare NHS Trust
Sponsor class: OTHER
First posted: 2009-02-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patient Who Gained Remission From the Nephrotic Syndrome
timeFrame: 10-109 weeks
Secondary outcomes:
measure: Number of Patients Achieved Remission
timeFrame: 6-12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Imperial College London
name: Megan Griffith, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.