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

NCT03096275 | Completed Phase 3 DMC

• 1 other identifier: PUMCHCSTAR-006
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 7

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.

Conditions

Takayasu Arteritis

Keywords

Mycophenolate mofetil; Methotrexate; cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Proportion of patients with partial remission

  52 weeks

• Safety profile of MMF combined with MTX

  52 weeks

• Rate of complications

  52 weeks

Study Arms (2)

MMF+MTX+Glucocorticoids

EXPERIMENTAL

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; Drug: Glucocorticoids; Drug: MTX

CYC/AZA+Glucocoticoids

ACTIVE COMPARATOR

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

Drug: CYC; Drug: Glucocorticoids; Drug: AZA

Interventions

MMF DRUG

Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil

Also known as: Guangwei

MMF+MTX+Glucocorticoids

CYC DRUG

Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine

Also known as: huanlinxianan

CYC/AZA+Glucocoticoids

Glucocorticoids DRUG

Patients in the experimental group and comparator group were treated with Glucocorticoids and then gradually tapered

Also known as: qiangdisong

CYC/AZA+Glucocoticoids; MMF+MTX+Glucocorticoids

MTX DRUG

Patients in the experimental group are treated with Glucocorticoids combined with MTX and MMF

Also known as: jiaandieling

MMF+MTX+Glucocorticoids

AZA DRUG

Patients in the active comparator group were treated with Glucocorticoids combined with CYC followed by AZA

Also known as: liuzuopiaoling

CYC/AZA+Glucocoticoids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years-old either sex
• Patients with signed informed consent
• Fulfill the 1990 ACR Classification Criteria for TAK
• Patients with active disease according to GACTA criteria

You may not qualify if:

• Prior adverse events when treated with MTX that resulted in dose reduction or discontinuation;
• Prior treatment with MMF but failed response to MMF;
• Prior treatment with CYC but failed response to CYC;
• Renal dysfunction, defined as the estimated GFR \<80% or serum creatinine level higher than 1.5 times of upper normal limit;
• Severe liver function damage defined by serum ALT or AST higher than 2 times of the upper normal limits;
• Uncontrolled diabetes melitus;
• Uncontrolled heart failure at baseline;
• Active infection including tuberculosis , hepatitis B virus, hepatitis C virus, HIV or bacterial or fungal infection;
• Active upper GI bleeding in the past 3 months.

Sponsors & Collaborators

• Chinese SLE Treatment And Research Group: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (7)

Hebei Provincial Hospital

Shijiazhuang, Hebei, 050051, China

Location

the Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, 010050, China

Location

Xijing Hospital

Xian, Shanxi, 710032, China

Location

Beijing Chaoyang Hospital

Beijing, 100020, China

Location

Peking Union Medical College Hospital

Beijing, 100032, China

Location

Beijing Xuanwu Hospital

Beijing, 100053, China

Location

General Hospital of Tianjing Medical University

Tianjin, 300052, China

Location

Related 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.

  PMID: 1975175 BACKGROUND

• 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.

  PMID: 20054700 RESULT

• 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.

  PMID: 17332971 RESULT

• 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.

  PMID: 10068416 RESULT

• 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.

  PMID: 16221103 RESULT

• 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.

  PMID: 27924855 RESULT

MeSH Terms

Conditions

Takayasu Arteritis

Interventions

Glucocorticoids

Condition Hierarchy (Ancestors)

Aortic Arch Syndromes; Aortic Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Xinping Tian, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Patients were randomly assigned to two treatment arms and were treated for 12 months.

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 30, 2017
• Study Start: March 16, 2017
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: August 30, 2023

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)