Clinical trial NCT03096275: Comparison of Mycophenolate Mofetil and Cyclophosphamide for Active Takayasu's Arteritis
Official title: Comparison of the Efficacy of Mycophenolate Mofetil Combined With Methotrexate and Cyclophosphamide for the Treatment of Takayasu's Arteritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Takayasu Arteritis
Keywords: Mycophenolate mofetil
Methotrexate
cyclophosphamide
Lead sponsor: Chinese SLE Treatment And Research Group
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
First posted: 2017-03-30
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were randomly assigned to two treatment arms and were treated for 12 months.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with complete remission
timeFrame: 52 weeks
Secondary outcomes:
measure: Proportion of patients with partial remission
timeFrame: 52 weeks
measure: Safety profile of MMF combined with MTX
timeFrame: 52 weeks
measure: Rate of complications
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei Provincial Hospital
state: Hebei
city: Huhehaote
country: China
facility: the Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Xian
country: China
facility: Xijing Hospital
state: Shanxi
city: Beijing
country: China
facility: Beijing Chaoyang Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Beijing Xuanwu Hospital
city: Tianjin
country: China
facility: General Hospital of Tianjing Medical University
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xinping Tian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW Jr, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990 Aug;33(8):1129-34. doi: 10.1002/art.1780330811.
citation: Goel R, Danda D, Mathew J, Edwin N. Mycophenolate mofetil in Takayasu's arteritis. Clin Rheumatol. 2010 Mar;29(3):329-32. doi: 10.1007/s10067-009-1333-6.
citation: Shinjo SK, Pereira RM, Tizziani VA, Radu AS, Levy-Neto M. Mycophenolate mofetil reduces disease activity and steroid dosage in Takayasu arteritis. Clin Rheumatol. 2007 Nov;26(11):1871-5. doi: 10.1007/s10067-007-0596-z. Epub 2007 Feb 28.
citation: Daina E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases. Ann Intern Med. 1999 Mar 2;130(5):422-6. doi: 10.7326/0003-4819-130-5-199903020-00013.
citation: Ong LM, Hooi LS, Lim TO, Goh BL, Ahmad G, Ghazalli R, Teo SM, Wong HS, Tan SY, Shaariah W, Tan CC, Morad Z. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton). 2005 Oct;10(5):504-10. doi: 10.1111/j.1440-1797.2005.00444.x.
citation: Li J, Yang Y, Zhao J, Li M, Tian X, Zeng X. The efficacy of Mycophenolate mofetil for the treatment of Chinese Takayasu's arteritis. Sci Rep. 2016 Dec 7;6:38687. doi: 10.1038/srep38687.