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

Phase 4
Completed
Conditions
Systemic Lupus Erythematosus
Interventions
Registration Number
NCT01112215
Lead Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
240
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Enteric-coated Mycophenolate SodiumEnteric-Coated Mycophenolate Sodium-
azathioprineAzathioprine-
Primary Outcome Measures
NameTimeMethod
Obtention of complete remission24 months

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
NameTimeMethod
To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares.24 months

Trial Locations

Locations (1)

Vall d'Hebron Hospital

🇪🇸

Barcelona, Spain

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