Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy

Study Overview
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Brief Summary
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Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy Resistant to Conventional Treatments

Detailed Description
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Randomized, open, controlled, multicenter, clinical trial in patients with lupus nephritis previously treated with cyclophosphamide and mycophenolate. These patient can not have received Rituximab in the previous year. The number of patients estimated to reach statistical significance is 18 in each arm, a total sample size of 32 patients is needed. The hypothesis is that the alternative procedure (a second cycle of Rituximab)will reduce the relapse rate of lupus nephritis and the consequent deterioration of renal function. Besides it will reduce health care expenses(hospitalization, medication, hemodialysis and renal transplantation).

Official Title
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Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy Resistant to Conventional Treatments.

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both men and women between 18 and 70 years. Patient with active lupus nephritis, previously treated with cyclophosphamide and mycophenolate (sodium or mofetil), who have not received rituximab in the previous year. Women in childbearing age must have a pregnancy test in serum or urine negative and should use a contraceptive method suitable since at least 14 days prior to their inclusion in the study and up to 6 months after the last dose of the medication of the test. Informed consent form signed. Exclusion Criteria: Patients treated with rituximab in the previous years Active/sepsis serious infections Renal biopsy showing interstitial fibrosis and/or glomerular over 75%. Known neoplasia Heart failure with III/IV functional class Pregnancy Nursing Known anaphylaxis to the product History of hepatitis c History of tuberculosis Cardiovascular disease or uncontrolled hypertension Chronic hepatitis B Serious Cytopenia (granulocytes < 500/mm3, further < 10000/mm3) Immunodeficiency (CVI, immunoglobulins deficiency) Infection with HIV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rituximab (1 cycle)<br>1 cycle of Rituximab (4 i.v. infusions): Day 0: 375 mg/m2 Day 7: 375 mg/m2 Day 14: 375 mg/m2 Day 21: 375 mg/m2 | Biological: Rituximab<br>* Only one cycle of rituximab will be administered in this arm.<br>* Other names: Mabthera;|
| Experimental: Rituximab (2 cycles)<br>A second cycle of Rituximab First cycle of Rituximab (4 i.v. infusions): Day 0: 375 mg/m2 Day 7: 375 mg/m2 Day 14: 375 mg/m2 Day 21: 375 mg/m2 Second cycle of Rituximab (4 i.v. infusions, 6 months later) | Biological: Rituximab<br>* Only one cycle of rituximab will be administered in this arm.<br>* Other names: Mabthera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete or partial response in lupus nephritis | Complete response defined as: Glomerular Filtration Rate (GFR)≥ 60, 73 m2 (or decline to baseline or ± 15% of baseline in those with GFR <60 ml/min/1, 73m2). Proteinuria ≤ 0.5 g/24 hours. Inactive urine sediment (red cells, white cells, red cell casts according to local laboratory ranges). Serum albumin> 3 g / dl Partial response defined as: In patients with proteinuria ≥ 3.5 gr/24 h , decreased proteinuria <3.5 gr/24 hours. In patients with baseline proteinuria <3.5 gr/24 hours, reduced proteinuria> 50% of baseline. In both situations, stabilization (± 25%) or reduce of the Glomerular Filtration Rate. | Assessment at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function | Proportion of patients achieving a stabilization of renal function (Glomerular filtration rate of ± 25% over baseline or serum creatinine within normal range) | 24 months of follow-up | 
| Safety | Incidence of adverse events, serious adverse events and adverse events that led to the interruption of the study. | 24 months of follow-up | 
| Rescue medication | Need for immunosuppressive treatment added to the experimental pattern: - Mycophenolate - Azathioprine - Methotrexate | 24 months of follow-up | 
| Efficacy | Improvements in Selena-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score results | 24 months of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus Nephritis, remission, immunosuppressive treatment