Clinical trial NCT06498089: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Takayasu Arteritis
Keywords: Precise treatment
Clinical-molecular phenotype
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2024-07-12
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study was a randomized, controlled study, including two arms.
Primary purpose: TREATMENT

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will enter into the maintenance period and continue with the original regimen; if they do not meet this, they will be withdrawn from the study;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

Eligibility criteria: 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:

1. Presence of organ failure;
2. undergoing haemodialysis or major surgery (grade III and above) within 3 months;
3. the presence of other autoimmune diseases;
4. severe, progressive organ damage;
5. 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;
6. Have a history of malignancy;
7. Have any serious acute or chronic infection, including hepatitis B surface antigen positive, active tuberculosis.

Primary outcomes:
measure: Effectiveness rate
timeFrame: 6 months
Secondary outcomes:
measure: Effectiveness rate
timeFrame: 12 months
measure: Relapse rate
timeFrame: 12 months
measure: Time to the first relapse
timeFrame: 12 months
measure: Adverse events
timeFrame: 12 months
measure: Vascular imaging changes
timeFrame: 12 months
measure: Cytokine changes
timeFrame: 12 months
measure: Improvement of Visual Analog Score for pain
timeFrame: 12 months
measure: Improvement of 36-Item Short Form Survey
timeFrame: 12 months
measure: Improvement of Functional Assessment of Chronic Illness Therapy - Fatigue
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Lindi Jiang, PhD
role: STUDY_CHAIR
References: