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

Imperial College Healthcare NHS Trust

Status and phase: Completed; Phase 4

Conditions: Glomerulonephritis, Membranous

Treatments: Drug: tacrolimus; Drug: tacrolimus and mycophenolate mofetil

Study type: Interventional

Funder types: Other

Identifiers

NCT00843856

2008-001009-41 (EudraCT Number)

13HH1282

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

tacrolimus

Active Comparator group

Description:

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

Treatment:

Drug: tacrolimus

tacrolimus and mycophenolate mofetil

Active Comparator group

Description:

tacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenolate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L

Treatment:

Drug: tacrolimus and mycophenolate mofetil