Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03298698
Recruitment Status : Recruiting
First Posted : October 2, 2017
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Radboud University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Idiopathic Nephrotic Syndrome Minimal Change Disease Focal Segmental Glomerulosclerosis Drug: Rituximab Drug: Prednisone Phase 3

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome Unresponsive to 8 Weeks of High Dose Prednisone
Actual Study Start Date : August 22, 2018
Estimated Primary Completion Date : August 22, 2021
Estimated Study Completion Date : January 22, 2022


Arm Intervention/treatment
Experimental: Rituximab
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).
Drug: Rituximab
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).
Other Name: Mabthera

Active Comparator: Prednisone
Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks
Drug: Prednisone
Prednisone 1 mg/kg/day (max 80 mg/day) for 8 weeks
Other Name: Prednisolone




Primary Outcome Measures :
  1. Complete remission [ Time Frame: 8 weeks ]
    The proportion of patients reaching complete remission defined as proteinuria <0.3 g/day or < 300 mg/g


Secondary Outcome Measures :
  1. Partial remission [ Time Frame: 8 weeks ]
    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

  2. Late complete or partial remission [ Time Frame: 2-12 months ]
    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

  3. Time to remission [ Time Frame: 12 months ]
    Time between start of treatment and reaching partial or complete remission

  4. Time to relapse [ Time Frame: 12 months ]
    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

  5. Proportion of patients with a relapse [ Time Frame: 12 months ]
    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

  6. Proportion of patients treated with additional immunosuppressive drugs [ Time Frame: 12 months ]
    Proportion of patients treated with immunosuppressive drugs other than the assigned treatment with rituximab or prednisolone

  7. General health assessment [ Time Frame: at 2, 6, 9 and 12 months ]
    Difference in general health measured by RAND-36

  8. Quality of life measured with TAAQOL [ Time Frame: at 2, 6, 9 and 12 months ]
    Difference in quality of life measured with TNO-academisch Ziekenhuis Leiden Questionnaire for Adult's Health-Difference in Quality of Life

  9. Proportion of patients with adverse events [ Time Frame: at 2 and 12 months ]
    The proportion of patients with adverse events. Adverse events graded according to Common Terminology Criteria For Adverse Events (NCI-CTCAE v4.03)

  10. Cost-effectiveness analysis [ Time Frame: at 2, 6, 9 and 12 months ]
    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

  11. Cost-utility analysis [ Time Frame: at 2, 6, 9 and 12 months ]
    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.

  12. Difference in kidney function [ Time Frame: at 2 and 12 months ]
    Difference in creatinine clearance and estimated glomerular filtration rate

  13. Proportion of patients with an increase of baseline serum creatinine ≥ 50% [ Time Frame: at 2 and 12 months ]
    The percentage of patients with an increase > 50% of serum creatinine from baseline.

  14. Benefit-risk ratio 1 [ Time Frame: at 2 and 12 months ]
    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)

  15. Benefit-risk ratio 2 [ Time Frame: at 2 and 12 months ]
    Difference in the percentage of remissions (benefit) divided by the difference in the total number of adverse events (risk)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • 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 1 mg/kg/day (max 80 mg/day)
  • Idiopathic nephrotic syndrome caused by biopsy proven minimal change disease or focal segmental glomerulosclerosis

Exclusion Criteria:

  • Severe nephrotic syndrome with hypotension
  • Previous treatment with immunosuppressive medication other than prednisone
  • Treatment with prednisone > 10 weeks in last six months
  • Secondary form of FSGS or minimal change disease
  • Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc).
  • Patients infected with HIV or suffering from other active infections
  • Patients inoculated with a vaccine within 4 weeks prior to inclusion
  • Pregnancy, breast feeding, women with inadequate contraception
  • Malignancy
  • Kidney transplantation
  • Previous treatment with monoclonal antibodies within 2 years prior to inclusion
  • Neutrophils < 1.5 x 109/L and/or platelet counts < 75 x 109/L
  • Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
  • Active peptic ulcer
  • Known hypersensitivity to glucocorticoids
  • Insulin resistant diabetes mellitus
  • Treatment with carbamazepine, phenobarbital, phenytoin en rifampicin
  • Severe osteoporosis with vertebral fracture

Information from the National Library of Medicine

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): NCT03298698


Contacts
Layout table for location contacts
Contact: Jeroen Deegens, MD,PhD +31243614761 Jeroen.Deegens@radboudumc.nl

Locations
Layout table for location information
Netherlands
Radboud University Medical Center Recruiting
Nijmegen, Netherlands, 6500HB
Contact: Jeroen K Deegens, MD, PhD    +31243614761    Jeroen.Deegens@radboudumc.nl   
Contact: Jack F Wetzels, MD, PhD    +31243614761    Jack.Wetzels@radboudumc.nl   
Sponsors and Collaborators
Radboud University
Investigators
Layout table for investigator information
Principal Investigator: Jeroen K Deegens, MD,PhD Radboud University Nijmegen Medical center
Study Chair: Jack F Wetzels, MD, PhD Radboud University Nijmegen Medical Center

Layout table for additonal information
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03298698     History of Changes
Other Study ID Numbers: RSRNS17
First Posted: October 2, 2017    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Radboud University:
Idiopathic nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Rituximab
Randomized clinical trial
Additional relevant MeSH terms:
Layout table for MeSH terms
Nephrotic Syndrome
Nephrosis
Glomerulosclerosis, Focal Segmental
Nephrosis, Lipoid
Syndrome
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Nephritis
Prednisone
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal