Takayasu Arteritis Clinical Trial in China

Takayasu Arteritis Clinical Trial

— TACTIC  

Official title:

Comparison of the Efficacy and Safety of Leflunomide Versus Placebo Combine With the Basic Prednisone Therapy in Patients With Active Phase of Takayasu's Arteritis: a Randomized Controlled Double-blinded Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02981979
• Other study ID #: 2016ZSLC-06
• Status: Recruiting
• Phase: N/A
• Start date: December 2016
• Est. completion date: December 2022

Study information

• Verified date: June 2022
• Source: Shanghai Zhongshan Hospital
• Contact: Bingjie Wu, Doctor
• Phone: +86 135-6422-3680
• Email: wu.bingjie[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the efficacy and Safety of Leflunomide in Patients With Active Phase of Takayasu's Arteritis

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form;

2. Subjects who met the American College of Rheumatology 1990 classification criteria for Takayasu arteritis:

2.1 Age of onset =40 years; 2.2 Claudication of upper or lower extremities; 2.3 Decreased pulsation of 1 or both brachial arteries; 2.4 Difference of = 10 mmHg in systolic blood pressure between arms; 2.5 Bruit over subclavian arteries or aorta; 2.6 Angiography * showing a branch of the aorta stenosis or occlusion; Meeting more than 3 of 6 criteria suggests the diagnosis of Takayasu arteritis.

• Angiography in this study was replaced by vascular magnetic resonance angiography(MRA)or computed tomography angiography(CTA).

3. Males or females between the ages of 18 and 65 years;

4. All subjects agreed to have no childbearing plan during the clinical trial, and the results of serum or urine pregnancy test for females must be negative;

5. Evidence of disease in active phase during the past 3 months, meeting at least 2 of the following criteria:

5.1 There is a new onset of vascular ischemia ,in accordance with at least one of the following:

5.1.1 newly discovered difference of blood pressure between arms (systolic pulse pressure difference of at least = 10mmHg);

5.1.2 new onset of decreased pulsation of 1 or both brachial arteries;

5.1.3 other new manifestations of vascular ischemia;

5.2 Inflammatory abnormalities, meeting at least one of the following:

5.2.1 Erythrocyte sedimentation rate(ESR) level higher than the normal upper limit(others factors like infection are excluded);

5.2.2 high-sensitivity C-reactive protein(hsCRP)= 6mg/L or C-reactive protein(CRP)> 10mg/L;

5.3 Imaging examinations show abnormalities suggesting that disease is in active phase, meeting at least one of the following: 5.3.1 Vascular wall show enhanced signal on MRA(active inflammation);

5.3.2 enhanced CTA suggests new vascular lesions;

5.3.3 Color Doppler ultrasonography suggests vascular wall inflammation;

5.3.4 PET/CT suggests elevated SUV value on vascular wall;

5.4 Systemic symptoms that can not be explained by other causes: fever, fatigue or losing weight.

6. If the patient is taking prednisone or its equivalent before screening, the dose should not exceed 0.6mg/kg/d and keep stable for at least 4 weeks before the first dose of the trial treatment;

7. If the patient has previously received medication for Takayasu Arteritis, the withdrawal time before first dose of the trial treatment should meet:

7.1 Leflunomide: = 6 months. If cholestyramine is used at least for 11 days, the withdrawal time required = 4 weeks;

7.2 Cyclophosphamide = 8 weeks;

7.3 Azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, thalidomide, antimalarial or any other medication for Takayasu arteritis but not specifically allowed during the trial was not taken when the first dose of trial drugs were given;

7.4 Biological agents such as rituximab, IL-6 receptor antagonists, tumor necrosis factor inhibitors, etc.: = 3 months;

Exclusion Criteria:

1. Takayasu arteritis which only show lesions of vascular dilatation or aneurysm formation;

2. Takayasu arteritis patients who have received surgery related to revascularization for Takayasu arteritis (except percutaneoustransluminalangioplasty) within 3 months; or received percutaneoustransluminalangioplasty within 1 months;

3. Subjects with organ failure, meeting at least one of the following:

3.1 Cardiac function: New York Heart Association grade 4;

3.2 Glomerular filtration rate = 60ml/min;

3.3 Liver function: Child-pugh grade 2 and worse than grade 2;

3.4 High frequency of amaurosis (flare on 3 consecutive days);

3.5 Acute cerebral infarction or cerebral hemorrhage;

3.6 Blood pressure> 160/100mmHg;

4. Suffer from other autoimmune diseases (eg, ANCA-associated vasculitis, systemic lupus erythematosus, Behcet's disease, etc.) besides Takayasu arteritis;

5. Serious or progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurological, or other coexisting medical conditions that are not associated with Takayasu's arteries but may result in unacceptable risks;

6. Co-morbidities as asthma that may require the use of medium to high doses of glucocorticoids (prednisone = 10 mg/day or equivalent doses of prednisone equivalents) during the study period;

7. subjects with history of malignancy diseases;

8. Subjects with any serious acute or chronic infection;

9. Hepatitis B surface antigen positive or hepatitis B DNA positive;

10. Hepatitis C antibody positive;

11. Subjects with clinical or radiological or laboratory evidence of active tuberculosis;

12. Subjects with abnormal laboratory test results, meeting at least 1 of the following:

12.1 Subjects with serum alanine aminotransferase (ALT) or glutamic-oxalacetic transaminase(AST)=1.5 fold of the normal upper limit;

12.2 Blood white blood cell count =4×10^9 / L;

12.3 Platelet count =100 × 10^9 / L;

12.4 Hemoglobin =85g / L;

12.5 Other laboratory test abnormalities that may contribute to unacceptable risks for participants in this study;

13. Subjects who are allergic to any of the investigational drugs;

14. Use treatments and/or medication that are not allowed in this trial:

14.1 History of leflunomide treatment for at least 3 months but not effective;

14.2 Subjects who had undergone plasmapheresis or lymphocyte replacement or immunosorbent therapy in the last one year, or those who had planned to receive such treatments;

14.3 Patients who are willing to receive attenuated vaccine during the trial;

14.4 Subjects accepted or planned to have organ transplantation;

Related Conditions & MeSH terms

• Arteritis
• Takayasu Arteritis

Intervention

Drug:
• Leflunomide 10mg Tab
20mg per day for leflunomide group during the entire study; 20mg per day for control group during the maintenance therapy (start from the 25th week till the end of the study).
• Prednisone Acetate
basic therapy(start with 0.6mg/kg/d and maintained for 4 weeks, then reducing 5mg every 2 weeks until 10mg per day if the subject achieve clinical remission.)
• Placebos
used in control group during the induced remission therapy for 24 weeks.

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital	Beijing	Beijing
China	The first affiliated hospital of Nanchang University	Nanchang	Jiangxi
China	Renji Hospital	Shanghai	Shanghai
China	Zhongshan hospital, Fudan University	Shanghai	Shanghai
China	Shanxi Da Hospital	Taiyuan	Shanxi
China	Xinjiang Uygur Autonomous Region People's Hospital	Urumqi	Xinjiang
China	Xijing Hospital	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Jiang lindi

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants achieving clinical remission	Clinical remission is defined as follows: No systemic symptoms such as fever, fatigue and weight loss; without new onset of ischemic symptoms and ischemic signs; Serum Erythrocyte sedimentation rate(ESR)levels in normal range (if not, retest after 1 week, take the lower one into analyse); Subject achieving clinical remission should meet all these criteria above.	From the date of randomization until the end of induced remission therapy, assessed up to 24 weeks
Secondary	Time to achieve clinical remission		From the date of randomization until the date of first documented clinical remission, assessed up to 24 weeks
Secondary	Mean dose of prednisone in each group at the end of induced remission therapy		At the end of induced remission therapy, assessed up to 24 weeks
Secondary	Recurrence rate during leflunomide maintenance therapy	Recurrence is determined as follows:Kerr score>= 2 or do not meet two or more than two criteria of the clinical remission standard,and the results need to be reconfirm 28 days later.; Kerr score: 1) presence of systemic symptoms as fever, fatigue and weight loss (1'); 2)presence of ischemic symptoms or signs (1'); 3) abnormal serum ESR levels (1'); 4) progression or new site of vascular lesions on MRA or CTA compared to baseline(1').	From the beginning of maintenance therapy to the end of follow up, assessed up to 32 weeks(from the end of the 24th week till the end of the 56th week)
Secondary	Time to recurrence during leflunomide maintenance therapy		From the beginning of maintenance therapy (the 25th week) to the date of first documented recurrence, assessed up to 32 weeks
Secondary	Number of participants with adverse events related to leflunomide treatments	Adverse events include neutropenia, elevated serum level of liver enzymes(> 2 fold of normal upper limit), reproductive toxicity and infection	From the date of randomization until the end of this trial, assessed up to 56 weeks
Secondary	The changes of Doctor General Visual Analogue Scale at the end of 24 weeks and 56 weeks compared to baseline		From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks)
Secondary	The changes of participant self-reports at the end of 24 weeks and 56 weeks compared to baseline	Participant self-reports include Patients General Visual Analogue Scale, SF-36 quality of life questionnaire, and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale	From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks)
Secondary	The changes of biomarkers related to Takayasu's disease at the end of 24 weeks and 56 weeks compared to the baseline, including the whole blood cell RNA transcripts, and gene epigenetics.		From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks)
Secondary	Radiological changes including Magnetic Resonance Angiography or Computed Tomography Angiography at the end of 24 weeks and 56 weeks compared to the baseline		From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks)