Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
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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 |
- 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
- 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: | December 2013 |
| Estimated Primary Completion Date: | December 2012 (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 |
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| Spain | |
| Vall d'Hebron Hospital | Recruiting |
| Barcelona, Spain, 08035 | |
| Contact: JOSEP ORDI, MD-PhD 34934894047 | |
| Principal Investigator: Josefina Cortés-Hernández, MD-PhD | |
| 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: | March 23, 2012 |
| 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 Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Azathioprine Mycophenolate mofetil Mycophenolic Acid Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antibiotics, Antineoplastic Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013