Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: A Randomized Controlled Trial of Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy
Brief Summary: 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


Options:
A: Arm Label: Mycophenolate mofetil, low dose steroid; Type: EXPERIMENTAL; Interventions: Drug: Mycophenolate mofetil, low dose steroid | Arm Label: Cyclosporin, low dose steroid; Type: ACTIVE_COMPARATOR; Interventions: Drug: Cyclosporin, low dose steroid | Intervention Type: DRUG; Name: Mycophenolate mofetil, low dose steroid; Assigned to Arm(s): Mycophenolate mofetil, low dose steroid | Intervention Type: DRUG; Name: Cyclosporin, low dose steroid; Assigned to Arm(s): Cyclosporin, low dose steroid
B: Arm Label: Rituximab Treatment Arm; Type: ACTIVE_COMPARATOR; Interventions: Drug: Rituximab | Arm Label: Cyclosporine Treatment Arm; Type: ACTIVE_COMPARATOR; Interventions: Drug: Cyclosporine | Intervention Type: DRUG; Name: Rituximab; Assigned to Arm(s): Rituximab Treatment Arm | Intervention Type: DRUG; Name: Cyclosporine; Assigned to Arm(s): Cyclosporine Treatment Arm
C: Arm Label: active comparator; Type: ACTIVE_COMPARATOR; Interventions: Drug: symptomatic treatment (Converting Enzyme inhibitor, Angiotensin II, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin) | Arm Label: experimental; Type: EXPERIMENTAL; Interventions: Drug: experimental (Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab) | Intervention Type: DRUG; Name: symptomatic treatment (Converting Enzyme inhibitor, Angiotensin II, Anti-renin, Aldosterone antagonist diuretic, Beta blocker, Calcium inhibitor, statin); Assigned to Arm(s): active comparator | Intervention Type: DRUG; Name: experimental (Non Immunosuppressive Symptomatic Treatment (NIST) and Rituximab); Assigned to Arm(s): experimental
D: Arm Label: RITUXIMAB; Type: EXPERIMENTAL; Interventions: Drug: Rituximab | Arm Label: Corticosteroids and Cyclophosphamide; Type: ACTIVE_COMPARATOR; Interventions: Drug: Methylprednisolone, Drug: Cyclophosphamide | Intervention Type: DRUG; Name: Rituximab; Assigned to Arm(s): RITUXIMAB | Intervention Type: DRUG; Name: Methylprednisolone; Assigned to Arm(s): Corticosteroids and Cyclophosphamide | Intervention Type: DRUG; Name: Cyclophosphamide; Assigned to Arm(s): Corticosteroids and Cyclophosphamide

Answer: D