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

Takayasu Arteritis Clinical Trial

— CommittedTA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03096275
• Other study ID #: PUMCHCSTAR-006
• Status: Completed
• Phase: Phase 3
• Start date: March 16, 2017
• Est. completion date: November 11, 2022

Study information

• Verified date: April 2021
• Source: Chinese SLE Treatment And Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: November 11, 2022
• Est. primary completion date: November 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arteritis
• Takayasu Arteritis

Intervention

Drug:
• MMF
Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil
• CYC
Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine
• Glucocorticoids
Patients in the experimental group and comparator group were treated with Glucocorticoids and then gradually tapered
• MTX
Patients in the experimental group are treated with Glucocorticoids combined with MTX and MMF
• AZA
Patients in the active comparator group were treated with Glucocorticoids combined with CYC followed by AZA

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital	Beijing
China	Beijing Xuanwu Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	the Affiliated Hospital of Inner Mongolia Medical University	Huhehaote	Inner Mongolia
China	Hebei Provincial Hospital	Shijiazhuang	Hebei
China	General Hospital of Tianjing Medical University	Tianjin
China	Xijing Hospital	Xian	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Chinese SLE Treatment And Research Group	Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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 neph — View 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. — View Citation

Outcome

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