Multitarget Therapy for Idiopathic Membranous Nephropathy
Status:
Not yet recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
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.