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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
Sponsor:
Collaborator:
Ministry of Health, Spain
Information provided by (Responsible Party):
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT01765842
First received: January 3, 2013
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Lupus Nephritis
Biological: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of the Efficacy of Two Rituximab Treatment Regimens in Patients With Lupus Nephropathy Resistant to Conventional Treatments.

Resource links provided by NLM:


Further study details as provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Rate of complete or partial response in lupus nephritis [ Time Frame: Assessment at 12 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 24 months of follow-up ] [ Designated as safety issue: Yes ]
    Proportion of patients achieving a stabilization of renal function (Glomerular filtration rate of ± 25% over baseline or serum creatinine within normal range)

  • Safety [ Time Frame: 24 months of follow-up ] [ Designated as safety issue: Yes ]
    Incidence of adverse events, serious adverse events and adverse events that led to the interruption of the study.

  • Rescue medication [ Time Frame: 24 months of follow-up ] [ Designated as safety issue: Yes ]

    Need for immunosuppressive treatment added to the experimental pattern:

    1. - Mycophenolate
    2. - Azathioprine
    3. - Methotrexate

  • Efficacy [ Time Frame: 24 months of follow-up ] [ Designated as safety issue: Yes ]
    Improvements in Selena-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score results


Estimated Enrollment: 36
Study Start Date: November 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rituximab (1 cycle)

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
Only one cycle of rituximab will be administered in this arm.
Other Name: Mabthera
Experimental: Rituximab (2 cycles)

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
Only one cycle of rituximab will be administered in this arm.
Other Name: Mabthera

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).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765842

Contacts
Contact: María Jesús Castillo Palma, MD, PhD 00349550134 MAJECA@telefonica.net
Contact: Clara M. Rosso Fernández, MD 00349550134 claram.rosso.sspa@juntadeandalucia.es

Locations
Spain
San Cecilio Hospital Not yet recruiting
Granada, Spain, 18012
Contact: Norberto Ortego Centeno, MD, PhD    0034958023559    nortego@gmail.com   
Principal Investigator: Norberto Ortego Centeno, MD, PhD         
Juan Ramón Jiménez Hospital Not yet recruiting
Huelva, Spain, 21005
Contact: Ignacio Martín Suarez, MD, PhD    0034959016131    imsuarez@telefonica.net   
Principal Investigator: Ignacio Martín Suarez, MD, PhD         
Carlos Haya Hospital Not yet recruiting
Málaga, Spain, 29010
Contact: Enrique Ramón Garrido, MD, PhD    0034951290013    ederamongm2@gmail.com   
Principal Investigator: Enrique Ramón Garrido, MD, Phd         
Principal Investigator: Enrique Ramón Garrido, MD, PhD         
Virgen del Rocío, Hospital Recruiting
Seville, Spain, 41013
Contact: Clara M. Rosso Fernández, MD    0034955013414    claram.rosso.sspa@juntadeandalucia.es   
Principal Investigator: María Jesús Castillo Palma, PhD         
Sponsors and Collaborators
Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
Ministry of Health, Spain
Investigators
Study Chair: María Jesús Castillo Palma, PhD Virgen del Rocío Hospital
  More Information

No publications provided

Responsible Party: Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01765842     History of Changes
Other Study ID Numbers: RITULUP
Study First Received: January 3, 2013
Last Updated: January 8, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Iniciativa Andaluza en Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud:
Lupus Nephritis
remission
immunosuppressive treatment

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Glomerulonephritis
Immune System Diseases
Kidney Diseases
Lupus Erythematosus, Systemic
Urologic Diseases
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014