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

Chinese SLE Treatment And Research Group

Status and phase: Completed; Phase 3

Conditions: Takayasu Arteritis

Treatments: Drug: CYC; Drug: MMF; Drug: AZA; Drug: Glucocorticoids; Drug: MTX

Study type: Interventional

Funder types: Other

Identifiers

NCT03096275

PUMCHCSTAR-006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 138 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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138 participants in 2 patient groups

MMF+MTX+Glucocorticoids

Experimental group

Description:

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.

Treatment:

Drug: MTX

Drug: Glucocorticoids

Drug: MMF

CYC/AZA+Glucocoticoids

Active Comparator group

Description:

Patients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks

Treatment:

Drug: Glucocorticoids

Drug: AZA

Drug: CYC