Comparison of Mycophenolate Mofetil and Cyclophosphamide for Active Takayasu's Arteritis

Study Overview
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Brief Summary
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Takayasu's arteritis(TAK) is a rare systemic vasculitis which can cause ischemia or inflammation of the involved organs and increase the overall mortality rate.The traditional treatment of TAK is primarily empirical. The most commonly used drugs for treating active TAK are glucocorticosteroids(GC) and immunosuppressants. However, the genital toxicity of CYC has limited its long term use. In a pilot study carried out by the principal investigator of this study has shown that mycophenolate mofetil(MMF) combined with MTX is effective and with few adverse effects. The purpose of this prospective open-label study is to compare the efficacy and safety of GC+MMF+MTX with GC+CYC followed by GC+AZA for the treatment of active TAK. 150 patients with active TAK will be recruited and randomized in a 2:1 ratio to GC+MMF+MTX group and C+CYC and AZA group. Patients were followed for 52 weeks for efficacy and safety assessment.

Detailed Description
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Takayasu's arteritis(TAK) is a rare systemic vasculitis which mainly involves aorta and its major branches. However,it is more prevalent in countries and areas along the silk road.Young women at child-bearing age is the most prevalent population.It can cause ischemia or inflammation of the involved organs and increase the overall mortality rate.Although it may be lethal in some patients,it is not well studied due to the rareness of the disease.The traditional treatment of TAK is primarily empirical. The most commonly used drugs for treating active TAK are glucocorticosteroids(GC) and immunosuppressants including cyclophosphamide(CYC), methotrexate(MTX) and azathioprine(AZA) etc. However,no of these drugs have been well studied. In addition, the genital toxicity of CYC, the first line medication for active TAK, has become the major limitation for its long term use for a chronic disease like TAK. Therefore, new immunosuppressants with less toxicity,especially with much less genital toxicity and low malignancy risk is essentially necessary. In a pilot study carried out by the principal investigator of this study has shown that mycophenolate mofetil(MMF) combined with MTX is effective and with few adverse effects. The purpose of this prospective open-label study is to compare the efficacy and safety of GC+MMF+MTX with GC+CYC followed by GC+AZA for the treatment of active TAK. 150 patients with active TAK will be recruited and randomized in a 2:1 ratio to GC+MMF+MTX group and C+CYC and AZA group. Patients were followed for 52 weeks to assess the efficacy and safety.

Official Title
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Comparison of the Efficacy of Mycophenolate Mofetil Combined With Methotrexate and Cyclophosphamide for the Treatment of Takayasu's Arteritis

Conditions
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Takayasu Arteritis

Intervention / Treatment
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* Drug: MMF
* Drug: CYC
* Drug: Glucocorticoids
* Drug: MTX
* Drug: AZA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years-old either sex Patients with signed informed consent Fulfill the 1990 ACR Classification Criteria for TAK Patients with active disease according to GACTA criteria Exclusion Criteria: Prior adverse events when treated with MTX that resulted in dose reduction or discontinuation; Prior treatment with MMF but failed response to MMF; Prior treatment with CYC but failed response to CYC; Renal dysfunction, defined as the estimated GFR <80% or serum creatinine level higher than 1.5 times of upper normal limit; Severe liver function damage defined by serum ALT or AST higher than 2 times of the upper normal limits; Uncontrolled diabetes melitus; Uncontrolled heart failure at baseline; Active infection including tuberculosis , hepatitis B virus, hepatitis C virus, HIV or bacterial or fungal infection; Active upper GI bleeding in the past 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients were randomly assigned to two treatment arms and were treated for 12 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMF+MTX+Glucocorticoids<br>Patients were treated with Glucocorticoids combined with mycphenolate mofetil(MMF) as well as methotrexate(MTX) treatment for 52 weeks and were followed for 52 weeks. | Drug: MMF<br>* Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil<br>* Other names: Guangwei;Drug: Glucocorticoids<br>* Patients in the experimental group and comparator group were treated with Glucocorticoids and then gradually tapered<br>* Other names: qiangdisong;Drug: MTX<br>* Patients in the experimental group are treated with Glucocorticoids combined with MTX and MMF<br>* Other names: jiaandieling;|
| Active Comparator: CYC/AZA+Glucocoticoids<br>Patients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks | Drug: CYC<br>* Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine<br>* Other names: huanlinxianan;Drug: Glucocorticoids<br>* Patients in the experimental group and comparator group were treated with Glucocorticoids and then gradually tapered<br>* Other names: qiangdisong;Drug: AZA<br>* Patients in the active comparator group were treated with Glucocorticoids combined with CYC followed by AZA<br>* Other names: liuzuopiaoling;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with complete remission | The proportion of patients who reached the pre-defined criteria of complete remission in both groups | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with partial remission | Proportion of patients who reached the pre-defined partial remission criteria of the disease | 52 weeks | 
| Safety profile of MMF combined with MTX | Proportion of adverse events in both treatment groups | 52 weeks | 
| Rate of complications | Proportion of patients with complications in both treatment group | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mycophenolate mofetil, Methotrexate, cyclophosphamide