Effect of Pirfenidone on TA Fibrosis
ConditionTakayasu Arteritis
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-60
SponsorShanghai Zhongshan Hospital
About this trial
Takayasu arteritis is a severe vasculitis which could lead to significant disability and even death. While standard anti-inflammatory treatments can manage the systemic inflammation, they failed to stop a key driver of the disease: vascular fibrosis. This fibrosis could result in blood vessels thickening and narrowing, which continues to progress in many patients.
To tackle this critical treatment gap, the present project explores a new strategy. Building on pirfenidone's success in treating fibrosis in organs just like lungs and liver, along with promising early observations from our center, investigators believe adding this anti-fibrotic drug to standard therapy could improve vessel injury directly.
Therefore, investigators plan to conduct a clinical trial comparing pirfenidone with placebo in patients with Takayasu arteritis. The goal is to determine if this approach can successfully improve vascular injury and patient outcomes ultimately.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients who have signed the informed consents and meet the ACR 2022 classification criteria for Takayasu arteritis.
Male or female, age between 18 and 60 years.
Female patients must have a negative serum or urine pregnancy test and do not have pregnancy plans during the study period.
Within the 3 months prior to enrollment, the patient's treatment regimen must consist of glucocorticoids and immunosuppressants (methotrexate). Biological agents (IL-6R, TNF, or monoclonal antibody) might be used based on clinical need. Other targeted therapies (such as CD20 monoclonal antibodies, JAK inhibitors, etc.) or cell-based therapies (such as CAR-T or stem cell therapy) are not permitted.
Disqualifiers
Presence of autoimmune diseases or autoinflammatory diseases other than Takayasu arteritis (e.g., systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, etc.);
Use of antifibrotic drugs or drugs with potential antifibrotic properties (such as acetylcysteine, nintedanib, pirfenidone, etc.) within 6 months prior to enrollment, or participation in other clinical trials involving antifibrotic therapies;
Impaired liver function (elevated transaminases ALT/AST >2 times the upper limit of normal, or bilirubin exceeding the upper limit of normal), severe renal insufficiency (eGFR <15 mL/min/1.73m²), or requirement for psychotropic medications (excluding sleep medicine for sleep disorders);
Any severe, progressive, or uncontrolled concurrent hematological, gastrointestinal, pulmonary, cardiac, neurological, or other medical conditions unrelated to Takayasu arteritis which could pose unpredictable risks, in the investigator's judgment;
Trial design
Design model
Parallel
Treatments tested in this trial
Pirfenidone Capsules
Drugpirfenidone 400mg.tid.po, escalated to 600mg.tid.po if acceptable in patients.
Placebo
DrugPlacebo capsules for pirfenidone.
Treatment groups
92 Participants
are divided into 2 treatment groupsGroup A: placeboPlacebo comparator 1 intervention
Group B: pirfenidoneExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
the effectiveness of pirfenidone in the treatment of Takayasu arteritis compared to the placebo
Compared to placebo, the effectiveness of pirfenidone in the treatment of Takayasu arteritis is assessed with a composite endpoint. It indicates both clinical remission and imaging efficacy criterias must be met simultaneously, as follows: Clinical remission should meet all of the following criterias (①-④): * Absence of systemic symptoms such as fever, fatigue, or weight loss; * No new vascular symptoms or signs, and no worsening of pre-existing vascular symptoms; ③ No new ischemic symptoms or signs, and no worsening of pre-existing ischemic symptoms; ④ Normal erythrocyte sedimentation rate (if abnormal, non-disease activity factors must be excluded; a repeat test should be performed for evaluation); Note: If any of the following events occur in the CTCAE 5.0 grade increasing from baseline and reach grade 2 or higher, the case will be directly classified as not remission. These events include: ischemic stroke, syncope, intermittent claudication, and myocardial infarction.
Time frame
"From enrollment to the end of treatment at 6 months"Secondary outcomes
1
The radiographic response rate of pirfenidone in the treatment of Takayasu arteritis at 6th month, compared to placebo.
1. Imaging Effective: Vascular ultrasound or MRA confirms a ≥30% reduction in the thickness of the affected vessel wall compared to baseline, along with a ≥10% increase in vessel diameter. 2. Imaging Improvement: Vascular ultrasound or MRA confirms a \<30% reduction in the thickness of the affected vessel wall compared to baseline, along with a \<10% expansion of the stenotic vessel diameter compared to baseline. 3. Imaging Ineffective: Vascular ultrasound or MRA confirms any of the following: an increase in the thickness of the affected vessel wall compared to baseline, OR no expansion of the stenotic vessel diameter compared to baseline, OR the occurrence of an ischemic event.
Time frame
From enrollment to the end of treatment at 6 months2
Compared to placebo, the clinical remission rate of pirfenidone at the end of 6th month in the treatment of Takayasu arteritis.
Time frame
From enrollment to the end of treatment at 6 months3
Compared to placebo, the average dose of glucocorticoid at the end of 6th month in pirfenidone, in the treatment of Takayasu arteritis.
Time frame
From enrollment to the end of treatment at 6 months4
Compared to placebo, the incidence of ischemic events within 6 months for pirfenidone in the treatment of Takayasu arteritis.
Time frame
From enrollment to the end of treatment at 6 monthsLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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