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

Primary Purpose

Lupus Nephritis

Status
Terminated
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Fundación Pública Andaluza Progreso y Salud
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Nephritis, remission, immunosuppressive treatment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • San Cecilio Hospital
  • Carlos Haya Hospital
  • Virgen del Rocío, Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Rituximab (1 cycle)

Rituximab (2 cycles)

Arm Description

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

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
January 3, 2013
Last Updated
July 9, 2015
Sponsor
Fundación Pública Andaluza Progreso y Salud
Collaborators
Ministry of Health, Spain
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1. Study Identification

Unique Protocol Identification Number
NCT01765842
Brief Title
Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy
Acronym
RITULUP
Official Title
Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy Resistant to Conventional Treatments.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
The recruitment period has finished without reaching sample size
Study Start Date
November 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
December 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Pública Andaluza Progreso y Salud
Collaborators
Ministry of Health, Spain

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy Resistant to Conventional Treatments
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Lupus Nephritis, remission, immunosuppressive treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab (1 cycle)
Arm Type
Active Comparator
Arm Description
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
Arm Title
Rituximab (2 cycles)
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
Only one cycle of rituximab will be administered in this arm.
Primary Outcome Measure Information:
Title
Rate of complete or partial response in lupus nephritis
Description
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.
Time Frame
Assessment at 12 months
Secondary Outcome Measure Information:
Title
Renal function
Description
Proportion of patients achieving a stabilization of renal function (Glomerular filtration rate of ± 25% over baseline or serum creatinine within normal range)
Time Frame
24 months of follow-up
Title
Safety
Description
Incidence of adverse events, serious adverse events and adverse events that led to the interruption of the study.
Time Frame
24 months of follow-up
Title
Rescue medication
Description
Need for immunosuppressive treatment added to the experimental pattern: - Mycophenolate - Azathioprine - Methotrexate
Time Frame
24 months of follow-up
Title
Efficacy
Description
Improvements in Selena-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score results
Time Frame
24 months of follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
María Jesús Castillo Palma, PhD
Organizational Affiliation
Virgen del Rocío Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
San Cecilio Hospital
City
Granada
ZIP/Postal Code
18012
Country
Spain
Facility Name
Carlos Haya Hospital
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Virgen del Rocío, Hospital
City
Seville
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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