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Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Hospital Universitari Vall d'Hebron Research Institute
Sponsor:
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier:
NCT01112215
First received: April 26, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

Azathioprine is still considered the treatment of choice for the non-renal manifestations of systemic lupus erythematosus (SLE) with an estimated efficacy of 45%.Recently, several studies have demonstrated the efficacy of mycophenolate mofetil/enteric-coated mycophenolate sodium in those cases, but so far, no controlled, randomized comparative study between the two drugs has been conducted. The aim is to perform a randomized, controlled, phase III/IV study comparing enteric-coated mycophenolate (ECMs) with azathioprine for induction and maintenance therapy of the non-renal manifestations of SLE. Methods: Patients with non-renal SLE flares (SLEDAI≥6 and/or BILAG o 2B refractory to full doses of hydroxychloroquine and prednisolone (≥10 mg/d) or with relapsing flares will be included. Patients will be stratified according the flare severity (moderate (SLEDAI<12)-severe (SLEDAI≥12)) and randomized (1:1) into two groups of treatment, EMCs (2gr/d) or AZA (2-2.5mg/kg/d) according to TMPT levels for 6 months. Dose will be progressively tapered based on clinical response up to completing a year of treatment. The main aim is the percentage of complete remission achieved ((SLEDAI <4 and/or absence of any BILAG A o B) at week 12 and 24 for moderate and severe flares, respectively. Secondary objectives include evaluating the reduction in the steroid requirement, number of flares post-treatment, effect on the biological parameters, and impact on quality of life, damage and drug safety. To detect a 20% difference between the two drugs with a 80% statistical power (0.05 alpha error), considering a follow up loss of 20%, a total of 240 patients is required.


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: Azathioprine
Drug: Enteric-Coated Mycophenolate Sodium
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial to Evaluate the Efficacy of Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Induction and Maintenance of Remission of the Extra-renal Lupus Manifestations

Resource links provided by NLM:


Further study details as provided by Hospital Universitari Vall d'Hebron Research Institute:

Primary Outcome Measures:
  • Obtention of complete remission [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Complete remission will be defined by a SLEDAI<4 and/or absence of any BILAG A or B after 12 weeks of treatment


Secondary Outcome Measures:
  • To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 240
Study Start Date: December 2009
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: azathioprine Drug: Azathioprine
Initial dose of 2-2.5 mg/kg (according to TMTP levels) for 6 months according the severity of the flare with progressive tapering if complete remission has been obtained
Active Comparator: Enteric-coated Mycophenolate Sodium Drug: Enteric-Coated Mycophenolate Sodium
Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age>18 years
  • Fulfill at least 4 of the 11 criteria for the ACR classification
  • Any extra-renal flare with an SLEDAI>6 and/or one BILAG A or 2 B
  • Oral corticosteroids>10 mg/day and HCQ > 400 mg/day for at least 30 days prior to inclusion

Exclusion Criteria:

  • Presence of active renal disease
  • Previous intolerance or hypersensibility to any of the active components
  • Active infection
  • Unmeasurable levels of TMPT
  • Pregnancy
  • Presence of a severe flare that requires other immunosuppressive treatment for its control
  • Any Psychiatric or social condition that did not ensure the patient´s follow-up and patient´s collaboration
  • Previous treatment with EC-MPS or Azathioprine in the last 2 months
  • Previous treatment with biological therapy in the last 3 months for anti-TNF therapy or in the last year for anti-CD20 therapy
  • ALT or GPT >120 UI/mL non-lupus related in the last 30 days
  • Leucopenia <1000x10E6 non-lupus related in the last 30 days
  • Symptoms related to other medical conditions non-lupus related such as antiphospholipid syndrome.
  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: NCT01112215

Locations
Spain
Vall d'Hebron Hospital Recruiting
Barcelona, Spain, 08035
Contact: JOSEP ORDI, MD-PhD    34934894047      
Principal Investigator: Josefina Cortés-Hernández, MD-PhD         
Sponsors and Collaborators
Hospital Universitari Vall d'Hebron Research Institute
Investigators
Study Director: JOSEP ORDI-ROS, MD VALL D'HEBRON HOSPITAL
Principal Investigator: JOSEFINA CORTES HERNANDEZ, MD VALL D'HEBRON HOSPITAL
  More Information

No publications provided

Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier: NCT01112215     History of Changes
Other Study ID Numbers: 2008-008934-35
Study First Received: April 26, 2010
Last Updated: April 16, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Universitari Vall d'Hebron Research Institute:
SLE
non-renal manifestations

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Azathioprine
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014