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

Phase 3
Completed
Conditions
Takayasu Arteritis
Interventions
Drug: CYC
Drug: Glucocorticoids
Drug: AZA
Registration Number
NCT03096275
Lead Sponsor
Chinese SLE Treatment And Research Group
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
138
Inclusion Criteria
  1. Patients older than 18 years-old either sex
  2. Patients with signed informed consent
  3. Fulfill the 1990 ACR Classification Criteria for TAK
  4. Patients with active disease according to GACTA criteria
Exclusion Criteria
  1. Prior adverse events when treated with MTX that resulted in dose reduction or discontinuation;
  2. Prior treatment with MMF but failed response to MMF;
  3. Prior treatment with CYC but failed response to CYC;
  4. Renal dysfunction, defined as the estimated GFR <80% or serum creatinine level higher than 1.5 times of upper normal limit;
  5. Severe liver function damage defined by serum ALT or AST higher than 2 times of the upper normal limits;
  6. Uncontrolled diabetes melitus;
  7. Uncontrolled heart failure at baseline;
  8. Active infection including tuberculosis , hepatitis B virus, hepatitis C virus, HIV or bacterial or fungal infection;
  9. Active upper GI bleeding in the past 3 months.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MMF+MTX+GlucocorticoidsMMFPatients were treated with Glucocorticoids combined with mycphenolate mofetil(MMF) as well as methotrexate(MTX) treatment for 52 weeks and were followed for 52 weeks.
MMF+MTX+GlucocorticoidsGlucocorticoidsPatients were treated with Glucocorticoids combined with mycphenolate mofetil(MMF) as well as methotrexate(MTX) treatment for 52 weeks and were followed for 52 weeks.
MMF+MTX+GlucocorticoidsMTXPatients were treated with Glucocorticoids combined with mycphenolate mofetil(MMF) as well as methotrexate(MTX) treatment for 52 weeks and were followed for 52 weeks.
CYC/AZA+GlucocoticoidsCYCPatients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks
CYC/AZA+GlucocoticoidsGlucocorticoidsPatients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks
CYC/AZA+GlucocoticoidsAZAPatients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of patients with complete remission52 weeks

The proportion of patients who reached the pre-defined criteria of complete remission in both groups

Secondary Outcome Measures
NameTimeMethod
Safety profile of MMF combined with MTX52 weeks

Proportion of adverse events in both treatment groups

Proportion of patients with partial remission52 weeks

Proportion of patients who reached the pre-defined partial remission criteria of the disease

Rate of complications52 weeks

Proportion of patients with complications in both treatment group

Trial Locations

Locations (7)

General Hospital of Tianjing Medical University

🇨🇳

Tianjin, China

Hebei Provincial Hospital

🇨🇳

Shijiazhuang, Hebei, China

Peking Union Medical College Hospital

🇨🇳

Beijing, China

Beijing Xuanwu Hospital

🇨🇳

Beijing, China

Xijing Hospital

🇨🇳

Xian, Shanxi, China

Beijing Chaoyang Hospital

🇨🇳

Beijing, China

the Affiliated Hospital of Inner Mongolia Medical University

🇨🇳

Huhehaote, Inner Mongolia, China

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