Glomerulonephritis, Membranous
Conditions
Keywords
Glomerulonephritis
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.
Interventions
DRUGtacrolimus
tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml
tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenolate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L
Sponsors
Imperial College Healthcare NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patient Who Gained Remission From the Nephrotic Syndrome | 10-109 weeks | Efficacy of mycophenolate in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Achieved Remission | 6-12 months | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L
tacrolimus: tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml | 20 |
| 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
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 | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Tacrolimus | Tacrolimus and Mycophenolate Mofetil | Total |
|---|---|---|---|
| Age, Continuous | 55 years | 48 years | 51 years |
| Estimated glomerus filtration rate (GRF) | 109 mls/min/1.73m^2 | 121 mls/min/1.73m^2 | 115 mls/min/1.73m^2 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United Kingdom | 20 participants | 20 participants | 40 participants |
| Serum albumin | 17 g/L | 18 g/L | 17.5 g/L |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 7 / 20 | 3 / 20 |
Outcome results
Primary
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.
Time frame: 10-109 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tacrolimus | Number of Patient Who Gained Remission From the Nephrotic Syndrome | 8 Participants |
| Tacrolimus and Mycophenolate Mofetil | Number of Patient Who Gained Remission From the Nephrotic Syndrome | 8 Participants |
p-value: 0.7Fisher Exact
Secondary
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.
Time frame: 6-12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tacrolimus | Number of Patients Achieved Remission | 16 Participants |
| Tacrolimus and Mycophenolate Mofetil | Number of Patients Achieved Remission | 19 Participants |