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.
1. This study is a randomised, controlled, open-label, evaluator-blinded, multicentre clinical trial with a 14-month (56-week) study period: a 6-month (0-24 weeks) induction remission period and an 8-month (24-56 weeks) maintenance remission period; 2. Subjects with aortitis who meet the entry criteria will be randomised and divided 1:1 into the precision therapy group and the conventional therapy group. The precision therapy group will be stratified according to the clinical-molecular phenotypes, and at the end of 6 months, if subjects achieve clinical remission and the amount of GCs is reduced to 7.5 mg/day for 4 weeks, they will enter into the maintenance period and continue with the original regimen; if they do not meet this, they will be withdrawn from the study; 3. The study adopts a superiority design, the primary study objective is to assess the efficacy of the two groups at the end of six months, and the secondary study objectives are to assess the efficiency of the two groups at the end of 12 months, relapse rate, safety, cumulative hormone dose, vascular imaging changes, changes in cytokine profiles, etc. 4. According to their new-onset symptoms at baseline or within past three months, the patients were divided into two clinical phenotypes: ①constitutional type: patients with constitutional symptoms, such as fever, fatigue, weakness, and weight loss, without any symptoms of organ ischemia, and at least 4 of the following indicators were above normal upper limits: ESR, CRP, C3, PLT, IL-6, C4, IgG; ②vascular inflammation type: patients with vascular-associated symptoms, such as carotidynia, angina, dizziness, and limb claudication, regardless of the constitutional symptoms or ischemic symptoms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
124
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.
This drug will be used in the traditional arm. A dose of 15mg per week will be used.
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).
This drug will be used in the precise treatment arm. A sustained release tablet will be used (11mg per day).
This drug will be used in the precise treatment arm. A dose of 40mg (ih) will used every 2 weeks.
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGEffectiveness rate
Effectiveness is defined if patients meet the following three in criteria ①-④ and criteria ⑤. * No systemic symptoms such as fever, malaise, or wasting; * No new onset of vascular symptoms and signs; * Normal blood sedimentation (in case of abnormality, it is necessary to exclude non-disease active factors and to review and evaluate with the review value); ④ Imaging: no progression of primary vascular lesions or new vascular lesions; ⑤ Glucocorticoids are reduced to 7.5mg/day and maintained for at least 4 weeks.
Time frame: 6 months
Effectiveness rate
* No systemic symptoms such as fever, malaise, or wasting; * No new onset of vascular symptoms and signs; * Normal blood sedimentation (in case of abnormality, it is necessary to exclude non-disease active factors and to review and evaluate with the review value); ④ Imaging: no progression of primary vascular lesions or new vascular lesions; ⑤ Glucocorticoids are reduced to 5mg/day and maintained for at least 4 weeks.
Time frame: 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: * Systemic symptoms, such as fever, skeletal and muscular symptoms; * Blood sedimentation (erythrocyte sedimentation rate, ESR) \>20mm/H; ③ Characteristics of vascular ischaemia or inflammation: e.g. intermittent claudication, diminished or absent pulse, vascular murmur, vascular pain blood pressure asymmetry; ④Abnormalities of angiography.
Time frame: 12 months
Time to the first relapse
The first time to develop relapse during 12 months' treatment.
Time frame: 12 months
Adverse events
The occurrence of adverse events and the corresponding rate.
Time frame: 12 months
Vascular imaging changes
New vascular lesions, vascular thickness changes, vascular stenosis changes and vascular dilation changes upon MRA or CTA.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 12 months
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