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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01112215
• Other study ID #: 2008-008934-35
• Status: Completed
• Phase: Phase 4
• First received: April 26, 2010
• Last updated: October 3, 2016
• Start date: December 2009
• Est. completion date: December 2015

Study information

• Verified date: March 2015
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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
• Enteric-Coated Mycophenolate Sodium
Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

Locations

Country	Name	City	State
Spain	Vall d'Hebron Hospital	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Obtention of complete remission	Complete remission will be defined by a SLEDAI<4 and/or absence of any BILAG A or B after 12 weeks of treatment	24 months	No
Secondary	To evaluate the safety, improvement in biological parameters and reduction of number of extra-renal flares.		24 months	Yes