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

NCT ID: NCT03096275

Last Updated: 2023-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-16
• Study Completion Date: 2022-11-11

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.

Conditions

Takayasu Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

MMF

Intervention Type: DRUG

Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil

Glucocorticoids

Intervention Type: DRUG

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

MTX

Intervention Type: DRUG

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

CYC/AZA+Glucocoticoids

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

Group Type: ACTIVE_COMPARATOR

CYC

Intervention Type: DRUG

Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine

Glucocorticoids

Intervention Type: DRUG

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

AZA

Intervention Type: DRUG

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

Interventions

MMF

Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil

Intervention Type: DRUG

CYC

Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine

Intervention Type: DRUG

Glucocorticoids

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

Intervention Type: DRUG

MTX

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

Intervention Type: DRUG

AZA

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

Intervention Type: DRUG

Other Intervention Names

Guangwei; huanlinxianan; qiangdisong; jiaandieling; liuzuopiaoling

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: collaborator

Chinese SLE Treatment And Research Group

OTHER

Sponsor Role: lead

Responsible Party

Xinping Tian

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xinping Tian, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Hebei Provincial Hospital

Shijiazhuang, Hebei, China

the Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, China

Xijing Hospital

Xian, Shanxi, China

Beijing Chaoyang Hospital

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

Beijing Xuanwu Hospital

Beijing, , China

General Hospital of Tianjing Medical University

Tianjin, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 1975175 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20054700 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17332971 (View on PubMed)

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.

Reference Type: RESULT

PMID: 10068416 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16221103 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27924855 (View on PubMed)

Other Identifiers

PUMCHCSTAR-006

Identifier Type: -

Identifier Source: org_study_id