Multitarget Therapy for Idiopathic Membranous Nephropathy

NCT04424862 | Completed Phase 4

• 1 other identifier: Version 3 20200607
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief 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

• 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.

Conditions

Efficacy

Outcome Measures

Primary Outcomes (1)

• The composite of complete or partial remission at 12 months

  complete remission: proteinuria of no more than 0.3 g per 24 hours and a serum albumin level of at least 35 g per milliliter. Partial remission: a reduction in proteinuria of at least 50% from baseline plus final proteinuria between 0.3 g and 3.5 g per 24 hours regardless of creatinine clearance or the serum albumin level.

  Month 12

Secondary Outcomes (4)

• Composite of complete or partial remission at 6 months

  at momth 6

• Treatment failure

  at momth 6

• adverse events

  within 12 months

• Relapse

  within 12 months

Study Arms (2)

Multitarget Therapy

EXPERIMENTAL

The combined therapy with prednisone, ciclosporin and mycophenolate mofetil.

Drug: Prednisone, ciclosporin and mycophenolate mofetil

Control

ACTIVE COMPARATOR

Ponticelli Regimen

Drug: Ponticelli Regimen

Interventions

Prednisone, ciclosporin and mycophenolate mofetil DRUG

Multitarget Therapy

Multitarget Therapy

Ponticelli Regimen DRUG

Month 1: i.v. methylprednisolone (0.5 g) daily for three doses, then oral prednison (0.5 mg/kg/d, maximum dose 30mg/d) for 27 days Month 2: Oral cyclophosphamide (2.0 mg/kg/d, maximum dose 100mg/d) for 30 days Month 3: Repeat Month 1 Month 4: Repeat Month 2 Month 5: Repeat Month 1 Month 6: Repeat Month 2

Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (2)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Beijing Frienship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

MeSH Terms

Interventions

Prednisone; Cyclosporine; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Zongli Diao, MD

  Beijing Frienship Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: June 7, 2020
• First Posted: June 11, 2020
• Study Start: June 9, 2020
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2022
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

CN (2)