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Takayasu Arteritis Clinical Trial in China (TACTIC)

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ClinicalTrials.gov Identifier: NCT02981979
Recruitment Status : Unknown
Verified March 2018 by Jiang lindi, Shanghai Zhongshan Hospital.
Recruitment status was:  Recruiting
First Posted : December 5, 2016
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Jiang lindi, Shanghai Zhongshan Hospital

Tracking Information
First Submitted Date  ICMJE November 22, 2016
First Posted Date  ICMJE December 5, 2016
Last Update Posted Date February 19, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
Number of participants achieving clinical remission [ Time Frame: From the date of randomization until the end of induced remission therapy, assessed up to 24 weeks ]
Clinical remission is defined as follows:
  1. No systemic symptoms such as fever, fatigue and weight loss;
  2. without new onset of ischemic symptoms and ischemic signs;
  3. 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • Time to achieve clinical remission [ Time Frame: From the date of randomization until the date of first documented clinical remission, assessed up to 24 weeks ]
  • Mean dose of prednisone in each group at the end of induced remission therapy [ Time Frame: At the end of induced remission therapy, assessed up to 24 weeks ]
  • Recurrence rate during leflunomide maintenance therapy [ Time Frame: 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) ]
    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').
  • Time to recurrence during leflunomide maintenance therapy [ Time Frame: From the beginning of maintenance therapy (the 25th week) to the date of first documented recurrence, assessed up to 32 weeks ]
  • Number of participants with adverse events related to leflunomide treatments [ Time Frame: From the date of randomization until the end of this trial, assessed up to 56 weeks ]
    Adverse events include neutropenia, elevated serum level of liver enzymes(> 2 fold of normal upper limit), reproductive toxicity and infection
  • The changes of Doctor General Visual Analogue Scale at the end of 24 weeks and 56 weeks compared to baseline [ Time Frame: From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks) ]
  • The changes of participant self-reports at the end of 24 weeks and 56 weeks compared to baseline [ Time Frame: From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks) ]
    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
  • 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. [ Time Frame: From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks) ]
  • Radiological changes including Magnetic Resonance Angiography or Computed Tomography Angiography at the end of 24 weeks and 56 weeks compared to the baseline [ Time Frame: From the date of randomization until the end of induced remission therapy (24 weeks) and maintenance therapy (56 weeks) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Takayasu Arteritis Clinical Trial in China
Official Title  ICMJE 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
Brief Summary The purpose of this study is to investigate the efficacy and Safety of Leflunomide in Patients With Active Phase of Takayasu's Arteritis
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Takayasu Arteritis
Intervention  ICMJE
  • 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).
  • Drug: 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.)
  • Drug: Placebos
    used in control group during the induced remission therapy for 24 weeks.
Study Arms  ICMJE
  • Active Comparator: Leflunomide group
    Use Leflunomide 20mg qd po. for 24 weeks for induced remission therapy combine with the basic prednisone 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. If the subject has not achieve clinical remission,do not change prednisone dose). Subjects who have achieved clinical remission, with the prednisone dose reduced to 10mg within 20 weeks and maintained to the end of 24 weeks enter the maintenance therapy.The next 32 weeks for maintenance therapy use leflunomide combine with prednisone 10mg per day.
    Interventions:
    • Drug: Leflunomide 10mg Tab
    • Drug: Prednisone Acetate
  • Placebo Comparator: Control Group
    Use Placebo for 24 weeks for induced remission therapy(24 weeks) and use leflunomide 20mg qd po. for maintenance therapy in the next 32 weeks. Prednisone is used as basic therapy during the whole trial (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. Then maintain 10mg per day until the end of the study). All subjects in control group enter maintenance therapy.
    Interventions:
    • Drug: Leflunomide 10mg Tab
    • Drug: Prednisone Acetate
    • Drug: Placebos
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: December 1, 2016)
116
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02981979
Other Study ID Numbers  ICMJE 2016ZSLC-06
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jiang lindi, Shanghai Zhongshan Hospital
Study Sponsor  ICMJE Jiang lindi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lindi Jiang, Doctor Shanghai Zhongshan Hospital
PRS Account Shanghai Zhongshan Hospital
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP