A Randomized, Controlled, Open-label, Multicenter Clinical Trial Comparing 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

Обзор

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.

Подробное описание

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will enter into the maintenance period and continue with the original regimen; if they do not meet this, they will be withdrawn from the study; 3.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.

Вмешательства

• Препарат Prednisone
  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.
• Препарат Methotrexate
  This drug will be used in the traditional arm. A dose of 15mg per week will be used.
• Препарат Tocilizumab
  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).
• Препарат Tofacitinib
  This drug will be used in the precise treatment arm. A sustained release tablet will be used (11mg per day).
• Препарат Adalimumab
  This drug will be used in the precise treatment arm. A dose of 40mg (ih) will used every 2 weeks.

Первичные конечные точки

• Effectiveness rate [Срок оценки: 6 months]

Вторичные конечные точки (9)

• Effectiveness rate [Срок оценки: 12 months]
• Relapse rate [Срок оценки: 12 months]
• Time to the first relapse [Срок оценки: 12 months]
• Adverse events [Срок оценки: 12 months]
• Vascular imaging changes [Срок оценки: 12 months]
• Cytokine changes [Срок оценки: 12 months]
• Improvement of Visual Analog Score for pain [Срок оценки: 12 months]
• Improvement of 36-Item Short Form Survey [Срок оценки: 12 months]
• Improvement of Functional Assessment of Chronic Illness Therapy - Fatigue [Срок оценки: 12 months]

Критерии участия

Критерии включения

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.

Критерии исключения

• Presence of organ failure;
• undergoing haemodialysis or major surgery (grade III and above) within 3 months;
• the presence of other autoimmune diseases;
• severe, progressive organ damage;
• Subjects with other comorbidities that may result in the need for additional moderate to high doses of glucocorticoids (prednisone ≥ 10 mg/day or equivalent doses of prednisone equivalents) during the study period;
• Have a history of malignancy;
• Have any serious acute or chronic infection, including hepatitis B surface antigen positive, active tuberculosis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhongshan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT06498089 · B2024-200R

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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