This will be an open-label, randomized controlled trial which compares continued treatment with high dose prednisone (standard therapy) to treatment with rituximab in patients with minimal change disease or focal segmental glomerulosclerosis unresponsive to 8 weeks of high dose prednisone . patients either receive 2 doses of Rituximab 375 mg/m2 iv at time 0 and 14 days with termination of prednisone or standard therapy which consist of 8 additional weeks of high dose prednisone treatment.
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are important causes of idiopathic nephrotic syndrome. First-line treatment with high dose prednisone up to 16 weeks is associated with serious side effects. Especially if treatment continues for more than 8 weeks. Retrospective studies suggested that Rituximab may be more effective in patients unresponsive to 8 weeks of high dose prednisone. Treatment with rituximab was associated with a higher proportion of patients attaining remission of proteinuria and with fewer side effects. This will be an open-label, randomized controlled trial which compares continued treatment with high dose prednisone (standard therapy) to treatment with rituximab in patients with an idiopathic nephrotic syndrome due to biopsy proven MCD or FSGS age 18 years or older. All patients will be treated with high dose prednisone (1 mg/kg/day) for 8 weeks. Patients can be included in the trial in case of persistent persistent proteinuria ≥ 2 g/ 24 hours or a protein-to-creatinine ratio ≥ 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone Patients either receive 2 doses of Rituximab 375 mg/m2 iv at time 0 and 14 days with termination of prednisone or standard therapy which consist of 8 additional weeks of high dose prednisone treatment. In the Rituximab group, B-cells will be monitored weekly, and if no complete depletion is achieved, additional dose(s) of Rituximab will be given at a weekly interval (maximum of 2 additional doses) until complete B cell depletion. Expected duration of the follow-up is 12 months, consisting of 9 visits.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Rituximab: 375 mg/m2 intravenously on day 0 and day 14 B-cells will be monitored weekly, and if no complete depletion is achieved, additional dose(s) of Rituximab will be given at a weekly interval until complete B cell depletion (maximum of 2 additional doses).
Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks
Radboud University Medical Center
Nijmegen, Netherlands
RECRUITINGComplete remission
The proportion of patients reaching complete remission defined as proteinuria \<0.3 g/day or \< 300 mg/g
Time frame: 8 weeks
Partial remission
The proportion of patients reaching partial remission defined as proteinuria \< 3.5 g/24 h or \< 3.5 g/g and 50% lower than baseline proteinuria
Time frame: 8 weeks
Late complete or partial remission
The proportion of patients reaching complete remission defined as proteinuria \<0.3 g/day or \< 300 mg/g or The proportion of patients reaching partial remission defined as proteinuria \< 3.5 g/24 h or \< 3500 mg/g and 50% lower than baseline proteinuria
Time frame: 2-12 months
Time to remission
Time between start of treatment and reaching partial or complete remission
Time frame: 12 months
Time to relapse
The time between partial or complete remission and relapse (defined as urinary protein excretion to ≥3.5 g/24 h or ≥3.5 g/g creatinine
Time frame: 12 months
Proportion of patients with a relapse
The proportion of patients with relapse (defined as urinary protein excretion to ≥3.5 g/24 h or ≥3.5 g/g creatinine in patients who had at least attained a partial remission and the time to relapse
Time frame: 12 months
Proportion of patients treated with additional immunosuppressive drugs
Proportion of patients treated with immunosuppressive drugs other than the assigned treatment with rituximab or prednisolone
Time frame: 12 months
General health assessment
Difference in general health measured by RAND-36
Time frame: at 2, 6, 9 and 12 months
Quality of life measured with TAAQOL
Difference in quality of life measured with TNO-academisch Ziekenhuis Leiden Questionnaire for Adult's Health-Difference in Quality of Life
Time frame: at 2, 6, 9 and 12 months
Proportion of patients with adverse events
The proportion of patients with adverse events. Adverse events graded according to Common Terminology Criteria For Adverse Events (NCI-CTCAE v4.03)
Time frame: at 2 and 12 months
Cost-effectiveness analysis
Cost-effectiveness will be calculated by dividing the difference in costs by the difference in effectiveness (based on the number of patients in remission) derived from the two groups. The resulting cost-effectiveness ratio will be expressed as costs per one more patient in remission
Time frame: at 2, 6, 9 and 12 months
Cost-utility analysis
Cost-utility analysis will be calculated by dividing the difference in costs by the difference in Quality Adjusted Life Years (QALY's). QALY's will be derived from the EuroQol-5d-5L questionnaire.
Time frame: at 2, 6, 9 and 12 months
Difference in kidney function
Difference in creatinine clearance and estimated glomerular filtration rate
Time frame: at 2 and 12 months
Proportion of patients with an increase of baseline serum creatinine ≥ 50%
The percentage of patients with an increase \> 50% of serum creatinine from baseline.
Time frame: at 2 and 12 months
Benefit-risk ratio 1
Difference in the percentage of remissions (benefit) divided by the difference in adverse events grade 3 or 4, including Serious Adverse Events and Suspected Unexpected Serious Adverse Reaction (risk)
Time frame: at 2 and 12 months
Benefit-risk ratio 2
Difference in the percentage of remissions (benefit) divided by the difference in the total number of adverse events (risk)
Time frame: at 2 and 12 months
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