Clinical trial NCT04737343: Comparison of the Efficacy of Leflunomide and Azathioprine for the Maintenance Therapy of ANCA Associated Vasculitis
Official title: The Efficacy of Leflunomide for the Maintenance Therapy of ANCA Associated Vasculitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: ANCA Associated Vasculitis
Maintenance Therapy
Keywords: ANCA Associated Vasculits
Azathioprine
Leflunomide
Maintenance
Lead sponsor: Chinese SLE Treatment And Research Group
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: Affiliated Hospital of Jilin University, Changchun,China
name: Second Affiliated Hospital of Nanchang University
name: The First Affiliated Hospital of Anhui Medical University
name: Beijing Shijitan Hospital, Capital Medical University
name: The Affiliated Hospital of Inner Mongolia Medical University
name: First Affiliated Hospital of Kunming Medical University
name: Sichuan Province People's Hospital
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
First posted: 2021-02-03
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, open-label, control, non-inferiority study
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: the percentage of patients with major relapse in 18 months follow-up time
timeFrame: from inclusion to the end of the study, 18 months in total
Secondary outcomes:
measure: The rate of minor relapse of the AZA and LEF treatment group in 18 months.
timeFrame: from inclusion to the end of the study, 18 months in total
measure: The rate of adverse events and their severity in both LEF and AZA treated patients during 18 months of the study period.
timeFrame: from inclusion to the end of the study, 18 months in total
measure: Patients progress to ESRD at the end of the study
timeFrame: from inclusion to the end of the study, 18 months in total
Other outcomes:
Locations:
city: Hefei
country: China
facility: AnHui provincial hospital
state: Anhui
city: Hohhot
country: China
facility: the Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Kunming
country: China
facility: the Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Unione Mdecial College Hospital
name: Xinping Tian
role: PRINCIPAL_INVESTIGATOR
References: