Takayasu Arteritis Clinical Trial in China

NCT ID: NCT02981979

Last Updated: 2025-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-22
• Study Completion Date: 2022-11-22

Brief Summary

To investigate the efficacy and safety of Leflunomide (LEF) versus placebo combined with prednisone for active Takayasu arteritis (TAK) in Chinese population.

Detailed Description

Takayasu arteritis (TAK) is a rare form of large-vessel vasculitis, characterized by immune -induced vascular inflammation, resulting in the stenosis and occlusion of blood vessels [1]. TAK is observed predominantly in Asian females under 40 years of age [2, 3]. The stenosis or occlusion of blood vessels can cause severe ischemic events (e.g., acute myocardial infarction, stroke, death) involving multiple organs. Patients with TAK experience impaired quality of life [4] and face a significantly higher risk of death compared with that in the sex- and age-matched general population, with a standardized mortality ranging from 2.7 to 17.3 [5, 6, 7]. Thus, timely and efficacious treatment is important to improve the prognosis in such a young population.

Glucocorticoids (GCs) are the first-line therapy for active TAK [8, 9]. High-dose GCs are initially efficacious. However, disease recurrence can occur in approximately 60% patients during the GCs tapering [10, 11]. Prolonged use of GCs is associated with significant toxicity, including glucose-metabolism disorders, cardiovascular adverse events (AEs), and osteoporosis [12, 13]. Therefore, immunosuppressive therapy is required to minimize the dose and duration of GC exposure [8, 9]. Conventional immunosuppressants have been recommended as GC-tapering agents for active TAK, whereas biological agents are recommended in refractory cases [8, 9]. Most previous studies focused on TAK treatment have been observational, only five randomized clinical trials (RCTs) are found, among which, just one study reported the effect of conventional immunosuppressants mycophenolate [14, 15, 16, 17, 18]. Thus, high-quality evidence to support therapeutic options of conventional immunosuppressants is very limited.

Leflunomide (LEF) is a conventional immunosuppressant [19], which has shown satisfied GC-tapering effects in the treatment of giant cell arteritis, another large vessel vasculitis, in several observational studies [20, 21, 22]. In 2012, the first open-label study of 14 TAK patients demonstrated that 70% of patients could achieve at least partial clinical remission, and the GC dose could be reduced by 50% during LEF treatment [23]. Since then, several observational cohort or case-control studies have reported the efficacy of LEF for active TAK [24, 25, 26, 27, 28, 29]. A most recent study reported a comparable complete response rate of LEF (78%) versus adalimumab (88%) at 15-month follow-up [30]. Thus, LEF would be a promising alternative treatment for TAK, but evidence from RCTs is lacking.

We conducted this multicenter, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of LEF versus placebo combined with prednisone for active TAK, namely "Takayasu arteritis clinical trial in China" (TACTIC; ClinicalTrials.gov identifier: NCT02981979).

Conditions

Takayasu Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Leflunomide group

For the first 24 weeks, patients in the LEF group were treated with prednisone (0.6mg/kg/d, p.o.) and LEF (20mg/d, p.o.). The initial dose of prednisone was maintained for 4 weeks and then tapered by 5.0 mg every 2 weeks. The tapering of prednisone dose was determined by the investigators based on their assessment of disease activity. Two investigators formulated a tapering plan for the same time. If there were differences between the 2 investigators' perspectives, a third experienced senior rheumatologist (Lindi Jiang) made the final decision. Once the prednisone dose was reduced to 10 mg/d, this dose was maintained to the end of week 52.

By week 24, if clinical remission had been achieved, the patients proceeded to maintenance therapy with LEF (20 mg/day) from week 25. If the patient did not meet the criteria for clinical remission, unblinding was carried out: patients in the LEF group discontinued the study.

Group Type: ACTIVE_COMPARATOR

Leflunomide(LEF)

Intervention Type: DRUG

Leflunomide:

For LEF arm, 20mg per day, p.o. through the whole study. For placebo group, 20mg per day, p.o. from week 25 to week 52.

Prednisone Acetate Tablets

Intervention Type: DRUG

Prednisone (5mg/tab): basic therapy, start with 0.6mg/kg/d and maintained for 4 weeks, then reducing 5mg every 2 weeks until 10mg per day.

Control Group

For the first 24 weeks, patients in the placebo group received prednisone (0.6mg/kg/d, p.o.) and LEF simulator (2 tablets/d, p.o.). Patients were instructed to take tablets regularly. The initial dose of prednisone was maintained for 4 weeks and then tapered by 5.0 mg every 2 weeks. The tapering of prednisone dose was determined by the investigators based on their assessment of disease activity. Two investigators formulated a tapering plan for the same time. If there were differences between the 2 investigators' perspectives, a third experienced senior rheumatologist (Lindi Jiang) made the final decision. Once the prednisone dose was reduced to 10 mg/d, this dose was maintained to the end of week 52.

By week 24, if clinical remission had been achieved, the patients proceeded to maintenance therapy with LEF (20 mg/day) from week 25. If the patient did not meet the criteria for clinical remission, unblinding was carried out: patients in the placebo group switched to LEF (20 mg/day) .

Group Type: PLACEBO_COMPARATOR

Leflunomide(LEF)

Intervention Type: DRUG

Leflunomide:

For LEF arm, 20mg per day, p.o. through the whole study. For placebo group, 20mg per day, p.o. from week 25 to week 52.

Prednisone Acetate Tablets

Intervention Type: DRUG

Prednisone (5mg/tab): basic therapy, start with 0.6mg/kg/d and maintained for 4 weeks, then reducing 5mg every 2 weeks until 10mg per day.

Placebos

Intervention Type: DRUG

2 tabs/d used in placebo arm for the first 24 weeks.

Interventions

Leflunomide(LEF)

Leflunomide:

For LEF arm, 20mg per day, p.o. through the whole study. For placebo group, 20mg per day, p.o. from week 25 to week 52.

Intervention Type: DRUG

Prednisone Acetate Tablets

Prednisone (5mg/tab): basic therapy, start with 0.6mg/kg/d and maintained for 4 weeks, then reducing 5mg every 2 weeks until 10mg per day.

Intervention Type: DRUG

Placebos

2 tabs/d used in placebo arm for the first 24 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. new vascular ischemic manifestations/physical signs or systemic symptoms;

2. evaluated erythrocyte sedimentation rate (ESR) or high-sensitivity C reactive protein (hs-CRP) ≥6 mg/L or C reactive protein (CRP) ≥10 mg/L without other confounding factors (e.g., infection);

3. active vascular inflammation as indicated by contrast-enhanced computed tomography angiography (CTA), magnetic resonance angiography (MRA), color Doppler ultrasonography or positron emission tomography/CT (PET/CT); iii. Individuals should not receive LEF within 3 months before screening; iv. For individuals who received cyclophosphamide before screening, cyclophosphamide should be discontinued for ≥8 weeks; for patients who received a biological agent before screening, biological agents (e.g., tocilizumab, rituximab, and inhibitors of tumor necrosis factor) should be discontinued for ≥12 weeks; v. For patients who were taking prednisone (or its equivalent) before screening, the dose should be ≤0.6 mg/kg/day and the dose should be stable for ≥4 weeks; vi. Pregnancy should not be planned and a pregnancy test should be negative.

Exclusion Criteria

1. heart dysfunction: New York Heart Association grade IV;

2. renal dysfunction: estimated glomerular filtration rate ≤60 mL/min;

3. liver dysfunction: Child-Pugh grade ≥2;

4. neurologic severe ischemic event: amaurosis on 3 consecutive days, acute cerebral infarction, or cerebral hemorrhage;

5. uncontrolled blood pressure >160/100 mmHg; iv. Individuals had at least one following abnormal laboratory test results:

(1) alanine aminotransferase or aspartate transaminase ≥1.5-fold of the upper limit of normal in serum; (2) white blood cell count ≤4×109/L; (3) platelet count ≤100×109/L; (4) hemoglobin ≤85 g/L; v. Individuals had other types of autoimmune disease or uncontrolled asthma who need prednisone ≥10 mg/day, a history of malignant tumor or any serious acute/chronic infection, including positivity for hepatitis B surface antigen, hepatitis C antibody, or clinical/radiological/laboratory evidence of active tuberculosis; vi. Individuals who were allergic to any of the investigational drugs; vii. Individuals had at least one of the following unacceptable treatments or medications:

1. previous treatment with LEF for ≥3 months but not efficacious;

2. planning to receive an attenuated vaccine during the study period;

3. planning to undergo (or have undergone) organ transplantation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiang lindi

OTHER

Sponsor Role: lead

Responsible Party

Jiang lindi

Chief of Department of Rheumatology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lindi Jiang, Doctor

Role: STUDY_DIRECTOR

Fudan University

Locations

Beijing Anzhen Hospital

Beijing, Beijing Municipality, China

The first affiliated hospital of Nanchang University

Nanchang, Jiangxi, China

The First Hospital of China Medical University

Shenyang, Liaoning, China

Zhongshan hospital, Fudan University

Shanghai, Shanghai Municipality, China

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi

Ürümqi, Xinjiang, China

Countries

China

References

Sun Y, Wu B, Zhang W, Ma L, Kong X, Chen H, Jiang L. Comparison of the efficacy and safety of leflunomide versus placebo combined with basic prednisone therapy in patients with active disease phase of Takayasu arteritis: study protocol for a randomized, double-blinded controlled trial (Takayasu arteritis clinical trial in China: TACTIC). Ther Adv Chronic Dis. 2023 Mar 4;14:20406223231158567. doi: 10.1177/20406223231158567. eCollection 2023.

Reference Type: DERIVED

PMID: 36895331 (View on PubMed)

Other Identifiers

2016ZSLC-06

Identifier Type: -

Identifier Source: org_study_id