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

NCT ID: NCT01112215

Last Updated: 2016-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2015-12-31

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

azathioprine

Group Type: ACTIVE_COMPARATOR

Azathioprine

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Enteric-Coated Mycophenolate Sodium

Intervention Type: DRUG

Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

Interventions

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

Intervention Type: DRUG

Enteric-Coated Mycophenolate Sodium

Initial dose of 1440 mg/day for 6 months to be tapered progressively if complete remission had been obtained

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

JOSEP ORDI-ROS, MD

Role: STUDY_DIRECTOR

VALL D'HEBRON HOSPITAL

JOSEFINA CORTES HERNANDEZ, MD

Role: PRINCIPAL_INVESTIGATOR

VALL D'HEBRON HOSPITAL

Locations

Vall d'Hebron Hospital

Barcelona, Barcelona, Spain

Countries

Spain

References

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Reference Type: DERIVED

PMID: 33687069 (View on PubMed)

Ordi-Ros J, Saez-Comet L, Perez-Conesa M, Vidal X, Mitjavila F, Castro Salomo A, Cuquet Pedragosa J, Ortiz-Santamaria V, Mauri Plana M, Cortes-Hernandez J. Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1575-1582. doi: 10.1136/annrheumdis-2016-210882. Epub 2017 Apr 27.

Reference Type: DERIVED

PMID: 28450313 (View on PubMed)

Other Identifiers

2008-008934-35

Identifier Type: -

Identifier Source: org_study_id