Clinical trial NCT05102448: Comparison of Tofacitinib and Methotrexate in Takayasu's Arteritis
Official title: Comparison of the Efficacy and Safety of Tofacitinib and Methotrexate Based on Prednisone Therapy in Patients with Active Phase of Takayasu's Arteritis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Takayasu Arteritis
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2021-11-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate and compare the efficacy and safety of tofacitinib and methotrexate based on prednisone therapy in patients with Takayasu arteritis

Detailed description: Takayasu's arteritis (TAK), a chronic large vessel vasculitis, involves the aorta and its main branches. Glucocorticoids and immunosuppressants such as methotrexate, cyclophosphamide are common agents for TAK treatment. However, their effects for remission induction and relapse prevention are not satisfied. More effective agents for TAK treatment remain to be investigated. Tofacitinib (TOF) is a Jak inhibitor, which has been proved to be effective in multiple autoimmune diseases such as rheumatoid arthritis. Our preliminary real-world study also demonstrated a promising treatment effect of TOF in patients with TAK. But its efficacy and safety needs further verification. The present randomized controlled trial aimes to compare efficacy between methotrexate and tofacitinib in TAK treatment.

Eligibility criteria: Inclusion Criteria:

1. Patients met 1990 American College of Rheumatology (ACR) classification criteria or 2018 ACR classification criteria (draft) of TAK
2. Women or men aged 18-65
3. All patients agreed that there is no fertility plan during clinical trials, and the results of female serum or urinary pregnancy tests must be negative
4. Active TAK patients according to NIH disease activity criteria
5. All patients agreed to sign the informed consent

Exclusion Criteria:

1. Patients with organ failure who accord to one or more of the following conditions:

   I.Heart function New York class 4 II.Glomerular filtration rate ≤ 60ml/min III.Liver function Child grade 2 and above IV.High-frequency melanoma (attacks for 3 consecutive days) V.Acute cerebral infarction or cerebral hemorrhage VI.Blood pressure \> 160/100mmHg
2. Patients who received revascularization surgery related to the treatment of TAK within 3 months (except balloon dilatation); balloon dilatation or surgery unrelated to TAK within 1 month
3. Patients who have other autoimmune diseases (e.g. ANCA-associated vasculitis, systemic lupus erythematosus, Behcet's disease, etc.)
4. Patients with severe, progressive or uncontrolled comorbidities of kidney, liver, blood system, gastrointestinal, lung, heart, etc or other coexisting medical conditions that may exert unexpected risks
5. Patients with concomitant diseases, such as asthma, that may require additional medium to high doses of glucocorticoids (prednisone ≥ 10mg/ days or equivalent dose) during the study period
6. Patients with active infections with HBV, HCV, tuberculosis or other serious acute or chronic infections
7. Patients with malignancies
8. Patients with one or more of the following abnormal laboratory examinations I.Serum ALT or AST ≥ 1.5 times the normal upper limit; II.White blood cell count ≤ 4 × 109/L III.Platelet count ≤ 100x109/L IV.Hemoglobin \< 85g/L V.Other abnormal laboratory tests that may cause unacceptable risks
9. Patients allergic to the experimental drug
10. Patients who have ever failed to tofacitinib or methotrexate after 3 months' treatment in previous medical history

Primary outcomes:
measure: The effectiveness rate after 6 months' treatment
timeFrame: From the enrollment to the end of 6 months
Secondary outcomes:
measure: The remission rate with GCs 7.5mg qd at the end of 12 months
timeFrame: From the enrollment to the the end of 12 months
measure: Relapse free survival rate
timeFrame: From the enrollment to the the end of 12 month
measure: The cumulative dosage of GCs during the whole period of 12-months follow-up
timeFrame: From the enrollment to the the end of 12 months
measure: Side effects rate
timeFrame: From the enrollment to the the end of 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Lindi Jiang
state: Shanghai
Study officials:
affiliation: Department of Rheumatology in Zhongshan hospital, Fudan University
name: Lindi Jiang, Ph.D., M.D.
role: STUDY_CHAIR
References: