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This study aimed to compare the efficacy and safety of a precision treatment regimen based on clinical-molecular phenotypes with a conventional treatment regimen in the treatment of patients with active Takayasu's arteritis based on a randomized, controlled, open-label, multicenter study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The precise therapy arm | Experimental | Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme:
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| The traditional therapy arm | Active Comparator | Patients will be given traditional treatment based on their clinical-molecular phenotype according to a predesigned scheme. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prednisone | Drug | This drug will be used in both arms. Patients' initial daily prednisone dose will be calculated according to their weights (0.6mg * weight(kg), maximum 50mg/day), and then tapered gradually during the study course. |
| Measure | Description | Time Frame |
|---|---|---|
| Effectiveness rate | Effectiveness is defined if patients meet the following three in criteria ①-④ and criteria ⑤.
| 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Effectiveness rate |
|
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Inclusion Criteria:
1) Meet the 2022 ACR/EULAR classification criteria for aortitis; 2) Women or men aged 18-65 years; 4) Be in active disease: a National Institutes of Health (NIH) score of ≥2; 5) Females with negative serum or urine pregnancy test results and no plans to have children during the clinical trial; (6) If the patient is taking prednisone or its equivalent, the pre-enrolment dose does not exceed 0.6 mg/kg/day and the dose has been stable for at least 4 weeks; 7) If the patient is receiving other medications for aortitis that are inconsistent with the assigned regimen, discontinuation is required for ≥4 weeks for methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, and tacrolimus; for leflunomide, discontinuation is required for 11 days if elimination methods are used (kolexanil or activated charcoal), or ≥8 weeks if elimination is not used; for cyclophosphamide, discontinuation is required for ≥6 months; for biologics, stopping for ≥ 3 weeks is required for etanercept, ≥ 4 weeks for IL-6 receptor antagonists and tumour necrosis factor inhibitors, and ≥ 6 months for rituximab.
8)For patients with no obvious active tuberculosis lesions but elevated T-spot, it is recommended that infectious specialists evaluate them, and preventive anti-tuberculosis therapy should be performed first if necessary. After T-spot declines, researchers will assess the relevant risks before deciding whether they are suitable to participate in this study, and continue preventive anti-tuberculosis therapy for a total of 9 months.
9)For patients with HBV, if the viral replication was detected, it is recommended to take anti-viral treatment for 2-4 weeks, and researchers will evaluate whether they are suitable to participate in this study when no DNA replication is detected.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiufang Kong, PhD | Contact | +8618317070593 | kongxiufang2007@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Lindi Jiang, PhD | Fudan University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hospital, Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
No appliable
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This study was a randomized, controlled study, including two arms.
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The outcome assessor is blinded to the intervention.
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| Methotrexate | Drug | This drug will be used in the traditional arm. A dose of 15mg per week will be used. |
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| Tocilizumab | Drug | This drug will be used in the precise treatment arm. For patients in constitutional type a dose (8mg/kg weight) will be used every 2 weeks (iv drip) for 12 weeks, then a dose (8mg/kg weight) will be used every 4 weeks (iv drip). For patients in vascular inflammation type, a dose (8mg/kg weight) will be used every 4 weeks (iv drip). |
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| Tofacitinib | Drug | This drug will be used in the precise treatment arm. A sustained release tablet will be used (11mg per day). |
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| Adalimumab | Drug | This drug will be used in the precise treatment arm. A dose of 40mg (ih) will used every 2 weeks. |
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| 12 months |
| Relapse rate | The relapse is defined as disease re-activation after remission. Disease activity is assessed according to NIH criteria. NIH≥2 is considered active status. NIH criteria includes:
| 12 months |
| Time to the first relapse | The first time to develop relapse during 12 months' treatment. | 12 months |
| Adverse events | The occurrence of adverse events and the corresponding rate. | 12 months |
| Vascular imaging changes | New vascular lesions, vascular thickness changes, vascular stenosis changes and vascular dilation changes upon MRA or CTA. | 12 months |
| Cytokine changes | Changes of different cytokine profiles, including interleukin levels, chemotactic protein levels, fibrotic marker levels. The spepcific parameters include PTX3, IL6, IFN-g,TNFa, IL8, IL10, IL17, YKL40, CCL22, IL16, CCL2, CCL5, VEGF-A, PDGF-AB, FGF2, MMP1,MMP2, MMP3, MMP9,Leptin, PCSK5, FABP3, GPNMB. | 12 months |
| Improvement of Visual Analog Score for pain | Visual Analog Score for pain score ranges from 0 to 10, higher scores indicate a worse outcome. | 12 months |
| Improvement of 36-Item Short Form Survey | The 36-Item Short Form Survey score ranges from 0 to 800, higher scores indicate a better outcome. | 12 months |
| Improvement of Functional Assessment of Chronic Illness Therapy - Fatigue | The Functional Assessment of Chronic Illness Therapy - Fatigue score ranges from 0 to 52, higher socres indicate a worse outcome. | 12 months |
| ID | Term |
|---|---|
| D013625 | Takayasu Arteritis |
| ID | Term |
|---|---|
| D001015 | Aortic Arch Syndromes |
| D001018 | Aortic Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001167 | Arteritis |
| D014657 | Vasculitis |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D011241 | Prednisone |
| D005938 | Glucocorticoids |
| D008727 | Methotrexate |
| C502936 | tocilizumab |
| C479163 | tofacitinib |
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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