Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04424862 |
| Other study ID # |
Version 3 20200607 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
June 9, 2020 |
| Est. completion date |
February 3, 2022 |
Study information
| Verified date |
February 2022 |
| Source |
Beijing Friendship Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Membranous nephropathy (MN) is one of the commonest causes of nephrotic syndrome in adults,
idiopathic membranous nephropathy (IMN) accounts for 70%-80% of all MN patients. There is no
standard specific treatment for IMN. Initial therapy should be supportive and involves
restricting dietary protein and sodium intake, controlling blood pressure, hyperlipidemia,
and edema. The best proven therapy for patients with IMN is combined use of corticosteroids
and cyclophosphamide. However, there are some potential risk of other serious side effects
associated with the use of cytotoxic agents, such as bone marrow toxicity, severe infections,
gonadal dysfunction, and the long-term risk of malignancy.
The ideal maintenance treatment scheme for patients with IMN requires not only a remission of
nephrotic syndrome but also, fewer adverse effects. Some retrospective study suggested that
multitarget therapy (prednisone+calcineurin inhibitors+mycophenolate mofetil) was effective
for refractory IMN. However, we cannot get confirmed conclusion from the previous study due
to the limitation of retrospective studies with small sample size.
In this prospective multicenter randomized trial, we compared the efficacy between
multitarget therapy and Ponticelli regimen.
Trial Aims and Hypothesis The specific aims of this trial are to test the hypothesis
1. that multitarget therapy is non-inferior to Ponticelli regimen in inducing long-term
remission (CR or PR) of proteinuria in patients with IMN.
2. that multitarget therapy reduces the number of relapses (efficacy in sustaining
remission) and increases the time to relapse when compared with treatment with
Ponticelli regimen.
3. that multitarget therapy has a better side-effect profile when compared with treatment
with Ponticelli regimen in patients with IMN.
Methods:
Patient Recruitment Inclusion and exclusion criteria are as follows.
Inclusion Criteria:
- Age: 18-70 years.
- Body weight: 50-90 kg.
- Patients with membranous nephropathy were eligible if their diagnosis was confirmed by
renal biopsy, with the biopsy sample examined by light, immunofluorescence, and electron
microscopy. Renal biopsy samples were reviewed by the two principal investigators and
two renal pathologists.
- IMN patients with moderate risk and have a decline of less than 50% in proteinuria
despite renin-angiotensin system blockade for at least 6 months before randomization.
OR, IMN patients with high risk or very high risk.
- Serum albumin < 30 g/L.
- eGFR by MDRD formula had to be ≥ 60 ml/min per 1.73 m2.
Exclusion criteria:
- Secondary MN, pregnancy, breastfeeding, immunosuppressive treatment in the 3 preceding
months, and active infectious disease.
- Hepatitis B serology included Hbs antigen and Hbs and Hbc antibodies. Patients with
active hepatitis B and those with past hepatitis B infection without anti-Hbs antibodies
will be excluded.
- Patients with reproductive demand will be excluded.
Randomization and Treatment Groups Once all entry criteria have been satisfied and confirmed,
patients will be randomized to treatment with multitarget therapy or Ponticelli regimen.
Multitarget therapy:
Combination with prednisone, ciclosporin and mycophenolate mofetil.
Ponticelli regimen:
Cyclical corticosteroid/alkylating-agent therapy for IMN. Outcomes Primary outcome: The
primary clinical outcome was the composite of complete or partial remission at 12 months.
Secondary outcome: the composite of complete or partial remission at 6 months; complete
remission at 6 months; and adverse events, relapse.
Description:
Membranous nephropathy (MN) is one of the commonest causes of nephrotic syndrome in adults,
idiopathic membranous nephropathy (IMN) accounts for 70%-80% of all MN patients. There is no
standard specific treatment for IMN. Initial therapy should be supportive and involves
restricting dietary protein and sodium intake, controlling blood pressure, hyperlipidemia,
and edema. The best proven therapy for patients with IMN is combined use of corticosteroids
and cyclophosphamide. However, there are some potential risk of other serious side effects
associated with the use of cytotoxic agents, such as bone marrow toxicity, severe infections,
gonadal dysfunction, and the long-term risk of malignancy.
The ideal maintenance treatment scheme for patients with IMN requires not only a remission of
nephrotic syndrome but also, fewer adverse effects. Some retrospective study suggested that
multitarget therapy (prednisone+calcineurin inhibitors+mycophenolate mofetil) was effective
for refractory IMN. However, we cannot get confirmed conclusion from the previous study due
to the limitation of retrospective studies with small sample size.
In this prospective multicenter randomized trial, we compared the efficacy between
multitarget therapy and Ponticelli regimen.
Trial Aims and Hypothesis The specific aims of this trial are to test the hypothesis
1. that multitarget therapy is non-inferior to Ponticelli regimen in inducing long-term
remission (CR or PR) of proteinuria in patients with IMN.
2. that multitarget therapy reduces the number of relapses (efficacy in sustaining
remission) and increases the time to relapse when compared with treatment with
Ponticelli regimen.
3. that multitarget therapy has a better side-effect profile when compared with treatment
with Ponticelli regimen in patients with IMN.
Methods:
Patient Recruitment Inclusion and exclusion criteria are as follows.
Inclusion Criteria:
- Age: 18-70 years.
- Body weight: 50-90 kg.
- Patients with membranous nephropathy were eligible if their diagnosis was confirmed by
renal biopsy, with the biopsy sample examined by light, immunofluorescence, and electron
microscopy. Renal biopsy samples were reviewed by the two principal investigators and
two renal pathologists.
- IMN patients with moderate risk and have a decline of less than 50% in proteinuria
despite renin-angiotensin system blockade for at least 6 months before randomization.
OR, IMN patients with high risk or very high risk.
- Serum albumin < 30 g/L.
- eGFR by MDRD formula had to be ≥ 60 ml/min per 1.73 m2.
Exclusion criteria:
- Secondary MN, pregnancy, breastfeeding, immunosuppressive treatment in the 3 preceding
months, and active infectious disease.
- Hepatitis B serology included Hbs antigen and Hbs and Hbc antibodies. Patients with
active hepatitis B and those with past hepatitis B infection without anti-Hbs antibodies
will be excluded.
- Patients with reproductive demand will be excluded.
Randomization and Treatment Groups Once all entry criteria have been satisfied and confirmed,
patients will be randomized to treatment with multitarget therapy or Ponticelli regimen.
Multitarget therapy:
The patients in the multitarget group continued to receive prednisone 1 mg/kg/d (maximum
dosage 60mg/d) for 2 weeks and then tapered by 5mg per week. When reduced to 30mg/d,
maintained for 1 month, and then tapered by 5 mg per month. When reduced to 20mg/d,
maintained for 2 months, and then tapered by 2.5 mg per two-month. When reduced to 5 mg/d,
maintained for 4 months.
Mycophenolate mofetil (1 g/d for 6 months and then tapered to 0.75 g/d for another 12 months,
and tapered 0.5g for another 12 months) Ciclosporin (initial dosage 100 mg/d, and adjusted
the dosage to maintain trough concentration at 80-120 ng/mL. If the patients get complete
remission during dosage adjustment period, then maintain the dosage, don't need to get to the
target trough concentration. (1) When the patients get complete remission, maintain the
dosage for 2 weeks, then tapered by 25mg/d per 3 months. When reduced to 50 mg/d, maintain
for 12 months, then tapered to 25mg/d for another 12 months. (2) When the patients only get
partial remission, maintain the target dosage for 12 months, and then adjust the dosage
followed "(1)". (3) When the patients no response, maintain the target dosage for 6 months,
if the decreased UTP < 25%, suggested change the therapy regimen. If the decreased UTP ≥ 25%,
maintain the dosage for another 6 months, then follow "(2)".
Ponticelli regimen:
Cyclical corticosteroid/alkylating-agent therapy for IMN. Outcomes Primary outcome: The
primary clinical outcome was the composite of complete or partial remission at 12 months.
Secondary outcome: the composite of complete or partial remission at 6 months; complete
remission at 6 months; and adverse events, relapse.
