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
- Conditions
- Takayasu Arteritis
- Interventions
- Registration Number
- NCT06498089
- Lead Sponsor
- Shanghai Zhongshan Hospital
- Brief Summary
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.
- Detailed Description
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will enter into the maintenance period and continue with the original regimen; if they do not meet this, they will be withdrawn from the study;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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 124
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description The precise therapy arm Prednisone Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX. The precise therapy arm Methotrexate Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX. The precise therapy arm Tocilizumab Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX. The precise therapy arm Tofacitinib Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX. The precise therapy arm Adalimumab Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX. The traditional therapy arm Prednisone Patients will be given traditional treatment based on their clinical-molecular phenotype according to a predesigned scheme. The traditional therapy arm Methotrexate Patients will be given traditional treatment based on their clinical-molecular phenotype according to a predesigned scheme.
- Primary Outcome Measures
Name Time Method Effectiveness rate 6 months 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.
- Secondary Outcome Measures
Name Time Method Relapse rate 12 months 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 to the first relapse 12 months The first time to develop relapse during 12 months' treatment.
Cytokine changes 12 months 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.
Effectiveness rate 12 months * 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.Improvement of 36-Item Short Form Survey 12 months The 36-Item Short Form Survey score ranges from 0 to 800, higher scores indicate a better outcome.
Vascular imaging changes 12 months New vascular lesions, vascular thickness changes, vascular stenosis changes and vascular dilation changes upon MRA or CTA.
Improvement of Visual Analog Score for pain 12 months Visual Analog Score for pain score ranges from 0 to 10, higher scores indicate a worse outcome.
Adverse events 12 months The occurrence of adverse events and the corresponding rate.
Improvement of Functional Assessment of Chronic Illness Therapy - Fatigue 12 months The Functional Assessment of Chronic Illness Therapy - Fatigue score ranges from 0 to 52, higher socres indicate a worse outcome.
Trial Locations
- Locations (1)
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China