Comparison of Tofacitinib and Methotrexate in Takayasu's Arteritis

NCT ID: NCT05102448

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2025-12-31

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.

Conditions

Takayasu Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Tofacitinib

Partcipants would be given one tablet of tofacitinib (5mg per tablet), twice per day, the treatment duration will last 12 months during the whole follow-up period.

Group Type: EXPERIMENTAL

Tofacitinib

Intervention Type: DRUG

1. Tofacitinib 5mg twice a day for 12 months;

2. Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day (maximum 60mg/day). (2) Glucocorticoids tapering: glucocorticoids is tapered after two weeks treatment and is tapered 5mg each 2 weeks to 10mg qd in the first 6 months if patients were in inactive status based on the NIH disease activity criteria. During the 6th to 12th month, glucocorticoids is tapered 2.5mg each 4 weeks until 7.5mg qd if patients were in inactive status based on the NIH disease activity criteria.

Methotrexate

Participates would be given tablets of methotrexate (2.5mg per tablet) 15mg each week, the treatment duration will last 12 months during the whole follow-up period.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

1. Methotrexate (15mg each week) for 12 months

2. Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day (maximum 60mg/day). (2) Glucocorticoids tapering: glucocorticoids is tapered after two weeks treatment and is tapered 5mg each 2 weeks to 10mg qd in the first 6 months if patients were in inactive status based on the NIH disease activity criteria. During the 6th to 12th month, glucocorticoids is tapered 2.5mg each 4 weeks until 7.5mg qd if patients were in inactive status based on the NIH disease activity criteria.

Interventions

Tofacitinib

1. Tofacitinib 5mg twice a day for 12 months;

2. Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day (maximum 60mg/day). (2) Glucocorticoids tapering: glucocorticoids is tapered after two weeks treatment and is tapered 5mg each 2 weeks to 10mg qd in the first 6 months if patients were in inactive status based on the NIH disease activity criteria. During the 6th to 12th month, glucocorticoids is tapered 2.5mg each 4 weeks until 7.5mg qd if patients were in inactive status based on the NIH disease activity criteria.

Intervention Type: DRUG

Methotrexate

1. Methotrexate (15mg each week) for 12 months

2. Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day (maximum 60mg/day). (2) Glucocorticoids tapering: glucocorticoids is tapered after two weeks treatment and is tapered 5mg each 2 weeks to 10mg qd in the first 6 months if patients were in inactive status based on the NIH disease activity criteria. During the 6th to 12th month, glucocorticoids is tapered 2.5mg each 4 weeks until 7.5mg qd if patients were in inactive status based on the NIH disease activity criteria.

Intervention Type: DRUG

Other Intervention Names

TOF; MTX

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jiang lindi

Ph.D, M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindi Jiang, Ph.D., M.D.

Role: STUDY_CHAIR

Department of Rheumatology in Zhongshan hospital, Fudan University

Locations

Lindi Jiang

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lindi Jiang, Ph.D., M.D.

Role: CONTACT

zsh-rheum@hotmail.com

021-64041990 ext. 2471

Xiufang Kong, Ph.D., M.D.

Role: CONTACT

kongxiufang2007@163.com

021-64041990 ext. 2471

Facility Contacts

Lindi Jiang, Ph.D

Role: primary

zsh-rheum@hotmail.com

86-02164041990

Other Identifiers

TACTIC-TM

Identifier Type: -

Identifier Source: org_study_id