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

Primary Purpose

ANCA Associated Vasculitis, Maintenance Therapy

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Leflunomide
Azathioprine Tablets
Sponsored by
Chinese SLE Treatment And Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ANCA Associated Vasculitis focused on measuring ANCA Associated Vasculits, Azathioprine, Leflunomide, Maintenance

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • AnHui provincial hospital
  • the Affiliated Hospital of Inner Mongolia Medical University
  • the Affiliated Hospital of Kunming Medical University
  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Azathioprine treatment arm

Leflunomide treatment arm

Arm Description

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

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.

Outcomes

Primary Outcome Measures

the percentage of patients with major relapse in 18 months follow-up time
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

The rate of minor relapse of the AZA and LEF treatment group in 18 months.
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.
The rate of adverse events and their severity in both LEF and AZA treated patients during 18 months of the study period.
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.
Patients progress to ESRD at the end of the study
Patients progress to ESRD at the end of the study

Full Information

First Posted
January 25, 2021
Last Updated
November 26, 2021
Sponsor
Chinese SLE Treatment And Research Group
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, First Affiliated Hospital of Kunming Medical University, Sichuan Province People's Hospital, Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT04737343
Brief Title
Comparison of the Efficacy of Leflunomide and Azathioprine for the Maintenance Therapy of ANCA Associated Vasculitis
Acronym
LEFAZAREM
Official Title
The Efficacy of Leflunomide for the Maintenance Therapy of ANCA Associated Vasculitis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
June 30, 2021 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese SLE Treatment And Research Group
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, First Affiliated Hospital of Kunming Medical University, Sichuan Province People's Hospital, Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ANCA Associated Vasculitis, Maintenance Therapy
Keywords
ANCA Associated Vasculits, Azathioprine, Leflunomide, Maintenance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
prospective, randomized, open-label, control, non-inferiority study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Azathioprine treatment arm
Arm Type
Active Comparator
Arm Description
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
Arm Title
Leflunomide treatment arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Leflunomide
Other Intervention Name(s)
Tuoshu for commericial name
Intervention Description
Patient will be treated with Leflunomide(Tuoshu, the commericial name) 30mg QD for 18 months
Intervention Type
Drug
Intervention Name(s)
Azathioprine Tablets
Intervention Description
Patients included into this study will be treated with Azathioprine tablets 100mg QD for 18 months.
Primary Outcome Measure Information:
Title
the percentage of patients with major relapse in 18 months follow-up time
Description
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
Time Frame
from inclusion to the end of the study, 18 months in total
Secondary Outcome Measure Information:
Title
The rate of minor relapse of the AZA and LEF treatment group in 18 months.
Description
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.
Time Frame
from inclusion to the end of the study, 18 months in total
Title
The rate of adverse events and their severity in both LEF and AZA treated patients during 18 months of the study period.
Description
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.
Time Frame
from inclusion to the end of the study, 18 months in total
Title
Patients progress to ESRD at the end of the study
Description
Patients progress to ESRD at the end of the study
Time Frame
from inclusion to the end of the study, 18 months in total

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients age 18 to 75 years, both genders can be included. 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. Patients must fulfill the 1990 ACR classification criteria of GPA, EGPA and 2012 modified Chapel Hill classification criteria of MPA. Patients have to be ANCA-positive at diagnosis or during the course of their disease. Patients must sign the informed consent. Exclusion Criteria: Patients with TPMT gene mutation； Patients who had been treated with either AZA or LEF but relapsed in the past; Patients who had been treated with either AZA or LEF but had to stop due to adverse events or intolerance; Patients who have planned for pregnancy in next 2 years; Patients with severe liver dysfunction(defined as the elevation of liver enzyme 3 times the upper limit or Child grade III) or ESRD； Patients with uncontrolled sever hypertension, diabetes, active bacteria or fungal infection; Patients with active hepatitis virus infection as well as patients who have active mycobacteria infection; Patients who are not eligible according to the judge of the principal investigators or site investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yunjiao Yang, MD
Phone
86-13671313079
Ext
8613671313079
Email
yangyunjiao81@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hanqi Wang, RN
Phone
86-15810927696
Ext
8613691165939
Email
tianxp6@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xinping Tian
Organizational Affiliation
Peking Unione Mdecial College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
AnHui provincial hospital
City
Hefei
State/Province
Anhui
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Wang, MD
Phone
86-15055148790
Email
wang_liy@aliyun.com
First Name & Middle Initial & Last Name & Degree
Xiangpei Li, MD
Phone
86-13515605909
Email
13515605909@126.com
Facility Name
the Affiliated Hospital of Inner Mongolia Medical University
City
Hohhot
State/Province
Inner Mongolia
ZIP/Postal Code
010050
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongbin Li, MD
Phone
13948536552
Email
hongbin.li@cstar.org.cn
First Name & Middle Initial & Last Name & Degree
Ning Tie, MD
Phone
13948610720
Email
tieting@126.com
Facility Name
the Affiliated Hospital of Kunming Medical University
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650032
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Xu, MD
Phone
13888566797
Email
jian.xu@cstar.org.cn
First Name & Middle Initial & Last Name & Degree
Shu Li, MD
Phone
15198785584
Email
gglis@126.com
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinping Tian, MD
Phone
86-13691165939
Email
tianxp6@126.com
First Name & Middle Initial & Last Name & Degree
Hanqi Wang, RN
Phone
86-15810927696
Email
wanghanqi06@163.com
First Name & Middle Initial & Last Name & Degree
XInping Tian, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
only patient clincial information coud be released to public

Learn more about this trial

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

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