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Comparison of the Efficacy of Leflunomide and Azathioprine for the Maintenance Therapy of ANCA Associated Vasculitis (LEFAZAREM)

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ClinicalTrials.gov Identifier: NCT04737343
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : November 30, 2021
Sponsor:
Collaborators:
Shanghai Zhongshan Hospital
Affiliated Hospital of Jilin University, Changchun,China
Second Affiliated Hospital of Nanchang University
The First Affiliated Hospital of Anhui Medical University
Beijing Shijitan Hospital, Capital Medical University
The Affiliated Hospital of Inner Mongolia Medical University
The First Affiliated Hospital of Kunming Medical College
Sichuan Province People's Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Information provided by (Responsible Party):
Xinping Tian, Peking Union Medical College Hospital

Study Description
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Brief Summary:
This study is a prospective, open-labelled, randomized, controlled,multi-center clincial trial. The aim of this study is to verify that the remission rate of patients treated with Leflunomide is not inferior to that of patients treated with Azathioprine.

Condition or disease Intervention/treatment Phase
ANCA Associated Vasculitis Maintenance Therapy Drug: Leflunomide Drug: Azathioprine Tablets Not Applicable

Detailed Description:

Background The basic theme of AAV is relapse and remission. The maintenance therapy of AAV aimed to reduce or prevent relapse is very challenge. Although many medications have been used for the maintenance of AAV, Leflunomide (LEF) has not studied thoroughly yet. So far, only one study tested the efficacy of LEF in the maintenance therapy for AAV. However, the sample size of this study is small, so large size clinical study is needed to clarify the role of LEF in the maintenance of AAV.

LEF is one of the most frequently prescribed DMARDs in the treatment of rheumatic diseases in China. It is cheap and widely available. Many experiences have been accumulated about its efficacy and safety in Chinese patients with rheumatic diseases. But there is no study to show its effectiveness in the reduction of the relapse of AAV in China. In this study, we try to compare the effectiveness of LEF and AZA, the gold standard for maintenance therapy, in the maintenance of AAV.

Objectives To verify that the effectiveness of LEF in reducing relapse is not inferior to AZA by comparing the relapse rate of LEF and AZA during the 18 month maintenance treatment of AAV.

Study Design This is a prospective, randomized, open-label, control, non-inferiority study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: prospective, randomized, open-label, control, non-inferiority study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Efficacy of Leflunomide for the Maintenance Therapy of ANCA Associated Vasculitis
Actual Study Start Date : June 30, 2021
Estimated Primary Completion Date : November 30, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vasculitis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Azathioprine treatment arm
Patients will be treated with Azathioprine 100mg QD for 18 months combined with rednisone. The dosage of prednisone is tapered in the study period but will be maintained at 7.5mg/d to the end of the study period.All included patients will be treated with TMPco 2 tablets everyday during the study period if not contraindicated or intoleran.t
 Drug: Azathioprine Tablets
Patients included into this study will be treated with Azathioprine tablets 100mg QD for 18 months.
Experimental: Leflunomide treatment arm
Patient will be treated with Leflunomide 30mg QD for 18 months combined with prednisone. The dosage of prednisone is tapered in the study period but will be maintained at 7.5mg/d to the end of the study period. All included patients will be treated with TMPco 2 tablets everyday during the study period if not contraindicated or intolerant.
 Drug: Leflunomide
Patient will be treated with Leflunomide(Tuoshu, the commericial name) 30mg QD for 18 months
Other Name: Tuoshu for commericial name


Outcome Measures
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Primary Outcome Measures :
  1. the percentage of patients with major relapse in 18 months follow-up time [ Time Frame: from inclusion to the end of the study, 18 months in total ]
    the percentage of patients with major relapse (re-appearance or worsening of disease with a BVAS >0 and involvement of at least one major organ, a life-threatening manifestation, or both) at month 18


Secondary Outcome Measures :
  1. The rate of minor relapse of the AZA and LEF treatment group in 18 months. [ Time Frame: from inclusion to the end of the study, 18 months in total ]
    The rate of minor relapse (reappearance or worsening of disease with a BVAS >0, not corresponding to a major relapse but requiring mild treatment intensification) of the AZA and LEF treatment group.

  2. The rate of adverse events and their severity in both LEF and AZA treated patients during 18 months of the study period. [ Time Frame: from inclusion to the end of the study, 18 months in total ]
    2. The rate of adverse events and their severity(Severe events were defined as the adverse events of grade 3 or 4, deaths caused by any cause, cancers, side effects that necessitate hospitalization) in both LEF and AZA treated patients during the study period.

  3. Patients progress to ESRD at the end of the study [ Time Frame: from inclusion to the end of the study, 18 months in total ]
    Patients progress to ESRD at the end of the study


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients age 18 to 75 years, both genders can be included.
  2. Patients who are newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or EGPA in complete remission after combined treatment with glucocorticoids and pulse cyclophosphamide or Rituximab. Remission is defined as a Birmingham Vasculitis Activity Score(BVAS version 3) of 0.
  3. Patients must fulfill the 1990 ACR classification criteria of GPA, EGPA and 2012 modified Chapel Hill classification criteria of MPA.
  4. Patients have to be ANCA-positive at diagnosis or during the course of their disease.
  5. Patients must sign the informed consent.

Exclusion Criteria:

  1. Patients with TPMT gene mutation；
  2. Patients who had been treated with either AZA or LEF but relapsed in the past;
  3. Patients who had been treated with either AZA or LEF but had to stop due to adverse events or intolerance;
  4. Patients who have planned for pregnancy in next 2 years;
  5. Patients with severe liver dysfunction(defined as the elevation of liver enzyme 3 times the upper limit or Child grade III) or ESRD；
  6. Patients with uncontrolled sever hypertension, diabetes, active bacteria or fungal infection;
  7. Patients with active hepatitis virus infection as well as patients who have active mycobacteria infection;
  8. Patients who are not eligible according to the judge of the principal investigators or site investigators.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04737343


Contacts
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Contact: Yunjiao Yang, MD 86-13671313079 ext 8613671313079 yangyunjiao81@163.com
Contact: Hanqi Wang, RN 86-15810927696 ext 8613691165939 tianxp6@126.com

Locations
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China, Anhui
AnHui provincial hospital Not yet recruiting
Hefei, Anhui, China
Contact: Li Wang, MD    86-15055148790    wang_liy@aliyun.com   
Contact: Xiangpei Li, MD    86-13515605909    13515605909@126.com   
China, Inner Mongolia
the Affiliated Hospital of Inner Mongolia Medical University Not yet recruiting
Hohhot, Inner Mongolia, China, 010050
Contact: Hongbin Li, MD    13948536552    hongbin.li@cstar.org.cn   
Contact: Ning Tie, MD    13948610720    tieting@126.com   
China, Yunnan
the Affiliated Hospital of Kunming Medical University Not yet recruiting
Kunming, Yunnan, China, 650032
Contact: Jian Xu, MD    13888566797    jian.xu@cstar.org.cn   
Contact: Shu Li, MD    15198785584    gglis@126.com   
China
Peking Union Medical College Hospital Recruiting
Beijing, China, 100032
Contact: Xinping Tian, MD    86-13691165939    tianxp6@126.com   
Contact: Hanqi Wang, RN    86-15810927696    wanghanqi06@163.com   
Sub-Investigator: XInping Tian, MD         
Sponsors and Collaborators
Chinese SLE Treatment And Research Group
Shanghai Zhongshan Hospital
Affiliated Hospital of Jilin University, Changchun,China
Second Affiliated Hospital of Nanchang University
The First Affiliated Hospital of Anhui Medical University
Beijing Shijitan Hospital, Capital Medical University
The Affiliated Hospital of Inner Mongolia Medical University
The First Affiliated Hospital of Kunming Medical College
Sichuan Province People's Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
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Principal Investigator: Xinping Tian Peking Unione Mdecial College Hospital
More Information
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Responsible Party: Xinping Tian, Professor of Medicine, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT04737343    
Other Study ID Numbers: CSTAR-006
First Posted: February 3, 2021    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: only patient clincial information coud be released to public

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xinping Tian, Peking Union Medical College Hospital:
ANCA Associated Vasculits
Azathioprine
Leflunomide
Maintenance
Additional relevant MeSH terms:
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Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases
Azathioprine
Leflunomide
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors