Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO)
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|ClinicalTrials.gov Identifier: NCT03018535|
Recruitment Status : Unknown
Verified May 2019 by Francesco Scolari, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia.
Recruitment status was: Active, not recruiting
First Posted : January 12, 2017
Last Update Posted : May 20, 2019
Idiopathic Membranous nephropathy (IMN) is an auto-immune glomerular disease. Recent studies suggest that circulating auto-antibodies against the podocyte surface antigens phospholipase A2 receptor1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) cause the disease in the majority of the patients. Additional autoantibodies, directed to podocyte neo-expressed cytoplasm proteins have been described, including aldose reductase (AR), Mn-superoxide dismutase (SOD2) and alpha-enolase (alpha-ENO).
The commonest presentation of IMN is nephrotic syndrome. Data from placebo arms of interventional studies show that 30-40% of the untreated patients with persistent nephrotic syndrome (NS) progress to end-stage renal disease (ESRD).
The best-validated treatment regimen of IMN is combination therapy with steroids and cyclophosphamide, capable to induce remission of protenuria in two-third of the patients.
Despite this evidence of efficacy, there are concerns about the use of cyclophosphamide, since it may be associated with adverse events, including bone marrow suppression, gonadal toxicity, infections and oncogenic effects. Thus, the availability of alternative therapies highly effective but with a greater safety profile is desirable.
Given the key role of IgG antibodies in IMN, B cell depletion may favourably impact the glomerular disease. The anti-CD20 monoclonal antibody Rituximab is a selective B cell depleting agent. There is evidence that Rituximab is effective in the treatment of other diseases in which B cells play a key role, such as ANCA-related vasculitis. Observational studies in IMN provided encouraging data; in addition, the drug seems well tolerated.
Head-to-head comparisons between Rituximab and steroid plus ciclophosphamide in randomized clinical trials are missing.
The investigators propose this study in order to test, in a randomized controlled trial, the hypothesis that Rituximab is more effective than cyclical steroid/alkylating-agent therapy in inducing remission in patients with IMN and NS undergoing the initial treatment. In addition, the levels of the above-mentioned pathogenetic autoantibodies will be measured at baseline and during treatment. Finally, the study will compare the safety profile of steroid plus cyclophosphamide and Rituximab by evaluating the rate and severity of adverse events
|Condition or disease||Intervention/treatment||Phase|
|Glomerulonephritis, Membranous||Drug: Rituximab Drug: Methylprednisolone Drug: Cyclophosphamide||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||76 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Controlled Trial of Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy|
|Study Start Date :||January 2012|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
1 g. IV of Rituximab on days 1 and 15
Rituximab,1 g IV, day 1 and day 15
Active Comparator: Corticosteroids and Cyclophosphamide
Month 1, 3 and 5: 1g IV methylprednisolone daily for 3 doses; oral methylprednisolone (0.4mg/kg/day) or prednisone (0.5/mg/kg/day); Month 2, 4 and 6: Oral Cyclophosphamide (2.0 mg/kg/day)
Methylprednisolone 1 g IV daily for 3 doses, then oral methylprednisolone (0.4 mg/kg/day) or oral prednisone (0.5mg/kg/day) for 27 days during Month 1, 3, 5.
Month 2, 4 and 6: Oral Cyclophosphamide (2.0 mg/kg/day) for 30 days
- change in probability of complete remission (proteinuria < 0.3 g/day) Primary Outcome Measures The primary outcome measure is the change in probability of complete remission (proteinuria < 0.3 g/day) at one year (see Design and power considerations). [ Time Frame: 1 year ]The primary outcome measure is the change in probability of complete remission (proteinuria < 0.3 g/day) at one year
- Change from baseline in proteinuria [ Time Frame: from randomization up to 36 months ]Change from baseline in proteinuria at 6,12, 18, 24 and 36 months following treatment
- CR (Complete Remission) or PR (Partial Remission: Reduction in UP of > 50% plus final UP ≤ 3.5 g but >0.3g ) [ Time Frame: from randomization up to 36 months ]CR (Complete Remission) or PR (Partial Remission) at 6, 12, 18, 24, and 36 months
- Estimated Glomerular filtration rate (MDRD formula) [ Time Frame: from randomization up to 36 months ]Estimated Glomerular filtration rate (MDRD formula) at 6, 12, 18, 24, and 36 months
- Serum creatinine level (mg/dl) [ Time Frame: from randomization up to 36 months ]Serum creatinine level (mg/dl) at 6, 12, 18, 24, and 36 months
- Frequency of and time to relapse of nephrotic syndrome [ Time Frame: up to 36 months ]Frequency of and time to relapse of nephrotic syndrome
- Frequency of auto-antibodies and its relation to therapy and proteinuria response in a subgroup of patients [ Time Frame: baseline and after treatment (day 3, month 1, 3, 6 , 6 and 12) ]Frequency of auto-antibodies and its relation to therapy and proteinuria response in a subgroup of patients at baseline and 3 days, 1 month, 3 months, 6 months and 12 months after treatment
- serious side effects: Death, Life-threatening event, Hospitalization, Disability in the patient's body function/structure or physical activity or quality of life, Congenital anomaly, Intervention to prevent permanent impairment or damage) [ Time Frame: up to 36 months ]serious side effects: Death, Life-threatening event, Hospitalization, Disability in the patient's body function/structure or physical activity or quality of life, Congenital anomaly, Intervention to prevent permanent impairment or damage.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03018535
|Division of Nephrology, Montichiari Hospital, ASST Spedali Civili di Brescia|
|Montichiari, Brescia, Italy, 25018|
|Principal Investigator:||FRANCESCO SCOLARI, MD||Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia|