Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of iMN
- Conditions
- Idiopathic Membranous Nephropathy
- Interventions
- Registration Number
- NCT04743739
- Lead Sponsor
- Peking Union Medical College Hospital
- Brief Summary
The primary objective of this study is to determine whether or not cyclosporine (CsA) combined with RTX is more effective than RTX alone in the treatment of idiopathic membranous nephropathy (iMN).
- Detailed Description
To date, the first-line immunosuppressive therapy of iMN includes corticosteroids combined with cyclophosphamide or Rituximab (RTX) which has been used more and more widely due to superior safety profiles. But the long term remission rate of RTX monotherapy is only 60% and it takes effect relatively slowly.
2 pilot studies reported that the combination therapy of cyclosporine (CsA) and RTX had better efficacy for inducing remission for iMN, with the long term remission rate up to 85%. CsA and RTX may have synergistic effect in the treatment of iMN because they have different time of action and different effects on the immune system and podocytes.
Based on the previous rationale, the investigators designed this trial to determine whether combination of CsA and RTX is more effective than RTX alone in the treatment of iMN.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 126
- idiopathic MN with or without diagnostic biopsy
- Female, must be post-menopausal, sterile or have effective method of contraception
- must be off steroid or mycophenolate mofetil for >1 month and alkylating agents for > 6 months
- Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥3 months prior to randomization with controlled blood pressure or if patients is intolerant to ACEI/ARB
- proteinuria ≥4g/24h using the average from two 24-hour urine samples collected within 2 weeks of each other, and decreased ≤50% from baseline.
- estimated glomerular filtration rate (eGFR) ≥40ml/min/1.73m2
- presence of active infection or a secondary cause of MN
- diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
- pregnancy or breast feeding
- history of resistance to CsA or other calcineurin inhibitors(CNI), RTX or alkylating agents.
- Patients who previously achieved remission after treatment of CNI, RTX or alkylating agents but relapsed off CNI after 3 months, or relapsed off RTX or alkylating agents after 6 months, are eligible.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab monotherapy Rituximab Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to the CD19+ B cells count. Rituximab combined with cyclosporine Rituximab Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count. cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period. Rituximab combined with cyclosporine cyclosporine Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count. cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period.
- Primary Outcome Measures
Name Time Method complete remission (CR) or partial remission (PR) at 24 month 24 months after randomization complete or partial remission at 24 month. complete remission is defined as urine protein≤0.5g/24h and serum albumin≥3.5g/dl. Partial remission is defined as reduction in baseline urine protein ≥50% plus urine protein≤3.5g/24h but \>0.5g/24h
- Secondary Outcome Measures
Name Time Method complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month 6, 12, 18 months after randomization complete or partial remission on month 6, 12 and 18
complete remission (CR) on 6, 12, 18, 24 month 6, 12, 18, 24 months after randomization complete remission on month 6, 12, 18 and 24
Time to complete remission (CR) or partial remission (PR) from date of randomization until the date of first remission, assessed up to 24 months Time to complete or partial remission
Change of estimated glomerular filtration rate (eGFR) 24 months Change of eGFR from baseline to 24 months
Serum creatinine increase≥50 percent from baseline 24 months proportion of patients with increase of serum creatinine ≥50 percent from baseline
Proportion of patients with relapse 12，18，24 months Rate of relapse. Relapse is defined as development of nephrotic range proportion of patients with relapse. Relapse is defined as development of proteinuria\>3.5g/24h following CR or PR.
Anti-PLA2R titer baseline and 3, 6, 9, 12, 18, 24 months Auto-antibodies to the M-type phospholipase A2 receptor(PLA2R)
The number of CD19+B cells baseline and 3, 6, 9, 12, 18, 24 months CD19+ B cells
Adverse events through study completion until 24 months adverse events
Quality of life measured by kidney disease and quality of life (KDQOL-36) baseline, 12 and 24 month KDQOL-36 includes 36 questions which are scored positively (higher score indicating better quality of life) on a 0-100 scale using developer-recommended scoring.
Trial Locations
- Locations (7)
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Fuwai Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Beijing Tongren Hospital， Capital Medical University
🇨🇳Beijing, Beijing, China
Beijing Luhe Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Nanyang Nanshi Hospital, Henan University
🇨🇳Nanyang, Henan, China
The Seventh Affiliated Hospital, Sun Yat-sen University
🇨🇳Shenzhen, Shenzhen, China
The First Affiliated Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China