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

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

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.

Study Overview

• Status: Completed
• Conditions: Takayasu Arteritis
• Intervention / Treatment: Drug: MMF; Drug: Glucocorticoids; Drug: MTX; Drug: CYC; Drug: AZA

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.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100032
    • Peking Union Medical College Hospital
  • Beijing, China, 100020
    • Beijing ChaoYang Hospital
  • Beijing, China, 100053
    • Beijing Xuanwu Hospital
  • Tianjin, China, 300052
    • General Hospital of Tianjing Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • Hebei Provincial Hospital
  • Inner Mongolia
    • Huhehaote, Inner Mongolia, China, 010050
      • The Affiliated Hospital of Inner Mongolia Medical University
  • Shanxi
    • Xian, Shanxi, China, 710032
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chinese SLE Treatment And Research Group
• Collaborators: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Xinping Tian, MD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2017
• Primary Completion (Actual): November 11, 2022
• Study Completion (Actual): November 11, 2022

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (Actual): March 30, 2017

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Methotrexate; cyclophosphamide; Mycophenolate mofetil
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Vasculitis; Skin Diseases, Vascular; Aortic Diseases; Arteritis; Takayasu Arteritis; Aortic Arch Syndromes; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: PUMCHCSTAR-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No