Takayasu Arteritis Clinical Trial in China

NCT02981979 | Completed DMC

• 1 other identifier: 2016ZSLC-06
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Takayasu Arteritis

Keywords

Takayasu Arteritis; Leflunomide

Outcome Measures

Primary Outcomes (1)

• Achievement of clinical remission at week 24

  Clinical remission is defined as follows: (i) have no systemic symptoms (e.g., fever, fatigue, weight loss); (ii) have no new onset of ischemic symptoms and signs; (iii) have a normal level of erythrocyte sedimentation rate (ESR). If not achieved, the investigator excluded other influencing factors (especially infection), re-measure the ESR after 1 week, and use the re-examined value in the analyses. Subject achieving clinical remission should meet all these criteria above. The clinical remission rate and its difference between LEF and placebo group with 95% confidence interval (CI) at week 24 was estimated by Newcombe-Wilson procedure. If the lower limit of the 95%CI of the difference \>10%, it is considered that the efficacy of LEF is significantly superior to placebo.

  From the date of randomization until the end of induced remission therapy, assessed up to 24 weeks

Secondary Outcomes (7)

• Time to clinical remission

  From the date of randomization until the date of first documented clinical remission, assessed up to 24 weeks

• The mean prednisone dose at week 24

  At the end of induced remission therapy, assessed up to 24 weeks

• Achievement of clinical remission at week 52 in those who switched from placebo to LEF from week 25

  From the time of switch from placebo to LEF treatment (week 25), assessed up to week 52

• Disease recurrence through week 25 to week 52

  From the beginning of week 25 to the end of follow up, assessed up to week 52

• Time to recurrence

  from the beginning of achieving clinical remission to the date of the first documented disease recurrence, assessed up to 52 weeks

Study Arms (2)

Leflunomide group

ACTIVE COMPARATOR

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.

Drug: Leflunomide(LEF); Drug: Prednisone Acetate Tablets

Control Group

PLACEBO COMPARATOR

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) .

Drug: Leflunomide(LEF); Drug: Prednisone Acetate Tablets; Drug: Placebos

Interventions

Leflunomide(LEF) 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.

Control Group; Leflunomide group

Prednisone Acetate Tablets 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; Leflunomide group

Placebos DRUG

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

Control Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• heart dysfunction: New York Heart Association grade IV;
• renal dysfunction: estimated glomerular filtration rate ≤60 mL/min;
• liver dysfunction: Child-Pugh grade ≥2;
• neurologic severe ischemic event: amaurosis on 3 consecutive days, acute cerebral infarction, or cerebral hemorrhage;
• 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:
• previous treatment with LEF for ≥3 months but not efficacious;
• planning to receive an attenuated vaccine during the study period;
• planning to undergo (or have undergone) organ transplantation.

Sponsors & Collaborators

• Jiang lindi: lead

Study Sites (6)

Beijing Anzhen Hospital

Beijing, Beijing Municipality, China

Location

The first affiliated hospital of Nanchang University

Nanchang, Jiangxi, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, China

Location

Zhongshan hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi

Ürümqi, Xinjiang, China

Location

Related Publications (1)

• 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.

  PMID: 36895331 DERIVED

MeSH Terms

Conditions

Takayasu Arteritis

Interventions

Leflunomide; Prednisone

Condition Hierarchy (Ancestors)

Aortic Arch Syndromes; Aortic Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Lindi Jiang, Doctor

  Fudan University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants were assigned randomly (1:1) to treatment with LEF or placebo according to a computer-generated blocked randomization list. The randomization list, which assigns a unique randomization number to each treatment, was generated and kept sealed by a randomization administrator (independent of the trial conduct and data analysis). Randomization was masked to patients, investigators, clinical outcome monitors, project managers and statisticians. The packaging of the LEF and placebo was identical with labelled randomization number. For emergency use, investigators were given a sealed opaque envelope for each randomization number. If an envelope was opened, the time, date and reason for opening had to be recorded on the envelope and signed by the investigator. At the end of the trial, all envelopes were returned to the principal investigator unopened to confirm that masking had been maintained throughout the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of Department of Rheumatology

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: December 5, 2016
• Study Start: December 22, 2016
• Primary Completion: May 22, 2022
• Study Completion: November 22, 2022
• Last Updated: April 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)