Glomerulonephritis, Membranous
Conditions
Keywords
Idiopathic membranous nephropathy, Mycophenolate mofetil, Proteinuria, Renal function
Brief summary
Cyclosporin decreases proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a risk of side effects such as nephrotoxicity. The investigators plan to the study to evaluate whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effect.
Detailed description
Idiopathic membranous nephropathy is most common cause of glomerulonephritis in adults. Persistent high grade proteinuria or progressively decrease of renal function is a risk factor for end stage renal disease in idiopathic membranous nephropathy. It has been reported that cyclosporin in patients with idiopathic membranous nephropathy decreases proteinuria and improve renal function. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer side effect than cyclosporin. In this study patients with high risk group of progressive idiopathic membranous nephropathy will be treated with mycophenolate mofetil and low dose prednisone. The outcome will be compared to controls treated with cyclosporin and low dose prednisone.
Interventions
DRUGMycophenolate mofetil, low dose steroid
Mycophenolate Mofetil: Myconol capsule 250mg, Myconol 500 mg bid per day (less than 50kg), 750 \ 1000 mg bid per day (more than 50kg) Steroid: Methylprednisone 4mg tablet or Prednisolone 5mg tablet or Deflazacort 6mg tablet. Prednisolone dose: 0.15mg/kg up to a maximum dose of 15mg/day Duration: 48 weeks
DRUGCyclosporin, low dose steroid
Cyclosporin: Implanta soft cap (cyclosporin microemulsion) 25mg/100mg, starting dose of 4mg/kg per day and titrate according to investigator's decision based on cyclosporin trough level (100±50 ng/ml) Steroid: same dosage with active comparator goup Duration: 48 weeks
Sponsors
Hanmi Pharmaceutical Company Limited
Kyungpook National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with idiopathic membranous nephropathy 2. The duration of disease is less than twelve months 3. Patients with persistent proteinuria more than 8 grams per day 4. Patients who provided informed consent 5. The cases that satisfy more than three of following items even if proteinuria is less than 8 grams per day: * eGFR \< 60 ml/min/1.73m2 * Hypertension (BP above 140/90mmHg or BP above 120/80 in patients taking anti-hypertensive agents) * 24 hours urine protein or spot urine protein/creatinine ratio \> 5.0 g/day * Serum albumin (g/dL) \< 3.0 * Selectivity index \> 0.2
Exclusion criteria
1. Severe digestive organ disease 2. Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently. 3. Clinical history of treatment with other immunosuppressive medication 4. Probability of pregnancy, breast feeding woman 5. Uncontrolled hypertension (more than 160/100mmHg) 6. Uncontrolled systemic disease 7. Drug addiction or alcoholics within 6 months 8. eGFR is less than 30ml/min at screening 9. Abnormal liver function test (more than 3 times above compared with normal value) 10. Absolute neutrophil count \<1,500/mm3 or leukocyte \<2,500/mm3 or platelets \<100,000/mm3 11. Secondary membranous nephropathy 12. Expected life expectancy is less than 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Complete Remission | at 48 week after treatment | Complete remission: Reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL |
| Percentage of Partial Remission | at 48 week after treatment | Partial remission: Reduction in proteinuria to greater than 50 percent of initial values or absolute values of proteinuria between 200 mg and 3.5 g per day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Glomerular Filtration Rate (eGFR) | at 48 week after treatment | The change of eGFR mesured by Modification of Diet in Renal Disease (MDRD) study equation from baseline to 1 year after treatment |
| Relapse | For 48 weeks after treatment | A relapse is return of proteinuria to approximately 3.5g/day in patients who had previously undergone a complete or partial remission |
| Proteinuria | at 48 week after treatment | The change of proteinuria from baseline to 48 week after treatment |
| Side Effects | For 48 weeks after treatment | Any undesired effects of interventional drugs |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mycophenolate Mofetil, Low Dose Steroid Mycophenolate mofetil, low dose steroid: Mycophenolate Mofetil: Myconol capsule 250mg, Myconol 500 mg bid per day (less than 50kg), 750 \
1000 mg bid per day (more than 50kg) Steroid: Methylprednisone 4mg tablet or Prednisolone 5mg tablet or Deflazacort 6mg tablet. Prednisolone dose: 0.15mg/kg up to a maximum dose of 15mg/day Duration: 48 weeks | 21 |
| Cyclosporin, Low Dose Steroid Cyclosporin, low dose steroid: Cyclosporin: Implanta soft cap (cyclosporin microemulsion) 25mg/100mg, starting dose of 4mg/kg per day and titrate according to investigator's decision based on cyclosporin trough level (100±50 ng/ml) Steroid: same dosage with active comparator goup Duration: 48 weeks | 18 |
| Total | 39 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil, Low Dose Steroid | Cyclosporin, Low Dose Steroid | Total |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 10 | 52.7 years STANDARD_DEVIATION 10.9 | 55.4 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment South Korea | 21 participants | 18 participants | 39 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 16 Participants | 9 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 18 |
| other Total, other adverse events | 12 / 21 | 9 / 18 |
| serious Total, serious adverse events | 0 / 21 | 0 / 18 |
Outcome results
Primary
Percentage of Complete Remission
Complete remission: Reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL
Time frame: at 48 week after treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mycophenolate Mofetil, Low Dose Steroid | Percentage of Complete Remission | 4 Participants |
| Cyclosporin, Low Dose Steroid | Percentage of Complete Remission | 3 Participants |
Primary
Percentage of Partial Remission
Partial remission: Reduction in proteinuria to greater than 50 percent of initial values or absolute values of proteinuria between 200 mg and 3.5 g per day
Time frame: at 48 week after treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mycophenolate Mofetil, Low Dose Steroid | Percentage of Partial Remission | 12 Participants |
| Cyclosporin, Low Dose Steroid | Percentage of Partial Remission | 9 Participants |
Secondary
Estimated Glomerular Filtration Rate (eGFR)
The change of eGFR mesured by Modification of Diet in Renal Disease (MDRD) study equation from baseline to 1 year after treatment
Time frame: at 48 week after treatment
Secondary
Proteinuria
The change of proteinuria from baseline to 48 week after treatment
Time frame: at 48 week after treatment
Secondary
Relapse
A relapse is return of proteinuria to approximately 3.5g/day in patients who had previously undergone a complete or partial remission
Time frame: For 48 weeks after treatment
Secondary
Side Effects
Any undesired effects of interventional drugs
Time frame: For 48 weeks after treatment