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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Glomerulonephritis, Membranous

Intervention / Treatment
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* Drug: tacrolimus
* Drug: tacrolimus and mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tacrolimus<br>Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L | Drug: tacrolimus<br>* tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml<br>* Other names: prograff;|
| Active Comparator: tacrolimus and mycophenolate mofetil<br>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<br>* tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L<br>* Other names: cellcept;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glomerulonephritis