Back to resultsComparison of Tofacitinib and Methotrexate in Takayasu's Arteritis
Primary Purpose
Takayasu Arteritis
Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tofacitinib
Methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for Takayasu Arteritis
Eligibility Criteria
Inclusion Criteria:
- Patients met 1990 American College of Rheumatology (ACR) classification criteria or 2018 ACR classification criteria (draft) of TAK
- Women or men aged 18-65
- 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
- Active TAK patients according to NIH disease activity criteria
- All patients agreed to sign the informed consent
Exclusion Criteria:
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
- 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
- Patients who have other autoimmune diseases (e.g. ANCA-associated vasculitis, systemic lupus erythematosus, Behcet's disease, etc.)
- 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
- 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
- Patients with active infections with HBV, HCV, tuberculosis or other serious acute or chronic infections
- Patients with malignancies
- 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
- Patients allergic to the experimental drug
- Patients who have ever failed to tofacitinib or methotrexate after 3 months' treatment in previous medical history
Sites / Locations
- Lindi JiangRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tofacitinib
Methotrexate
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
The effectiveness rate after 6 months' treatment
The effectiveness rate equals to patients who achieved this goal /patients at the end of 6 months. The effectiveness was defined as satisfying three of the following 1)-4) criteria and the 5) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging; 5) GCs is tapered to 10mg qd and this dosage is maintained for 4 weeks.
Secondary Outcome Measures
The remission rate with GCs 5mg qd at the end of 12 months
Ratio of patients who achieved remission with GCs 5mg qd at the end of 12 months. The remission is defined as satisfying three of the following 1)-4) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging. It is required that GCs 5mg qd should be maintained at least for four weeks.
The remission rate with GCs 0mg qd at the end of 12 months
Ratio of patients who achieved remission with GCs 0mg qd at the end of 12 months. The remission is defined as satisfying three of the following 1)-4) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging. It is required that GCs 0mg qd should be maintained at least for four weeks.
Relapse free survival rate
Ratio of patients without relapse after achieving remission during the 12 months follow-up
The cumulative dosage of GCs during the whole period of 12-months follow-up
The cumulative dosage = Sum of doses of prednisone （or equivalents） each day
Side effects rate
Ratio of patients with side effects. All the kinds of adverse event related to the treatment and the disease itself will be recorded.
Full Information
NCT ID
NCT05102448
First Posted
October 19, 2021
Last Updated
October 19, 2021
Sponsor
Shanghai Zhongshan Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05102448
Brief Title
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
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Zhongshan Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Takayasu Arteritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
76 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tofacitinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Methotrexate
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tofacitinib
Other Intervention Name(s)
TOF
Intervention Description
Tofacitinib 5mg twice a day for 12 months;
Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/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 disuse if patients were in inactive status based on the NIH disease activity criteria.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
MTX
Intervention Description
Methotrexate (15mg each week) for 12 months
Basic treatment with prednisone: (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/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 disuse if patients were in inactive status based on the NIH disease activity criteria.
Primary Outcome Measure Information:
Title
The effectiveness rate after 6 months' treatment
Description
The effectiveness rate equals to patients who achieved this goal /patients at the end of 6 months. The effectiveness was defined as satisfying three of the following 1)-4) criteria and the 5) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging; 5) GCs is tapered to 10mg qd and this dosage is maintained for 4 weeks.
Time Frame
From the enrollment to the end of 6 months
Secondary Outcome Measure Information:
Title
The remission rate with GCs 5mg qd at the end of 12 months
Description
Ratio of patients who achieved remission with GCs 5mg qd at the end of 12 months. The remission is defined as satisfying three of the following 1)-4) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging. It is required that GCs 5mg qd should be maintained at least for four weeks.
Time Frame
From the enrollment to the the end of 12 months
Title
The remission rate with GCs 0mg qd at the end of 12 months
Description
Ratio of patients who achieved remission with GCs 0mg qd at the end of 12 months. The remission is defined as satisfying three of the following 1)-4) criteria: 1) no systemic symptoms such as weakness, weight loss, etc; 2) no new ischemic symptoms or signs; 3) normal erythrocyte sedimentation rate (ESR); 4) no new vascular progression or new lesions upon imaging. It is required that GCs 0mg qd should be maintained at least for four weeks.
Time Frame
From the enrollment to the the end of 12 months
Title
Relapse free survival rate
Description
Ratio of patients without relapse after achieving remission during the 12 months follow-up
Time Frame
From the enrollment to the the end of 12 month
Title
The cumulative dosage of GCs during the whole period of 12-months follow-up
Description
The cumulative dosage = Sum of doses of prednisone （or equivalents） each day
Time Frame
From the enrollment to the the end of 12 months
Title
Side effects rate
Description
Ratio of patients with side effects. All the kinds of adverse event related to the treatment and the disease itself will be recorded.
Time Frame
From the enrollment to the the end of 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients met 1990 American College of Rheumatology (ACR) classification criteria or 2018 ACR classification criteria (draft) of TAK
Women or men aged 18-65
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
Active TAK patients according to NIH disease activity criteria
All patients agreed to sign the informed consent
Exclusion Criteria:
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
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
Patients who have other autoimmune diseases (e.g. ANCA-associated vasculitis, systemic lupus erythematosus, Behcet's disease, etc.)
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
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
Patients with active infections with HBV, HCV, tuberculosis or other serious acute or chronic infections
Patients with malignancies
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
Patients allergic to the experimental drug
Patients who have ever failed to tofacitinib or methotrexate after 3 months' treatment in previous medical history
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lindi Jiang, Ph.D., M.D.
Phone
021-64041990
Ext
2471
Email
zsh-rheum@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiufang Kong, Ph.D., M.D.
Phone
021-64041990
Ext
2471
Email
kongxiufang2007@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lindi Jiang, Ph.D., M.D.
Organizational Affiliation
Department of Rheumatology in Zhongshan hospital, Fudan University
Official's Role
Study Chair
Facility Information:
Facility Name
Lindi Jiang
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindi Jiang, Ph.D
Phone
86-02164041990
Email
zsh-rheum@hotmail.com
12. IPD Sharing Statement
Learn more about this trial
Comparison of Tofacitinib and Methotrexate in Takayasu's Arteritis
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