TOP-ILD study

JRCT ID: jRCTs071230004

Registered date:10/04/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Progressive pulmonary fibrosis
• Date of first enrollment: 17/05/2023
• Target sample size: 32
• Study type: Interventional

Intervention(s)

Day 1:Prednisolone (5 mg 2 tablets once daily) + tacrolimus (0.075 mg/kg twice daily) Started oral administration
Day 8:nintedanib (150 mg 2 capsules twice daily) is added.
Predonisolone, tacrolimus, and nintedanib will be administered for up to 52 weeks.

Outcome(s)

• Primary Outcome: Change in the rate of decline in %FVC (relative value) before and 24 weeks after treatment intervention

Secondary Outcome

Absolute change in FVC at 24 and 52 weeks (ml)
Change in the rate of decline in %FVC (relative value) decline slope before and 52 weeks after treatment intervention
Change in %DLco at 24 and 52 weeks (%) (absolute and relative values)
Safety
Overall survival
Time to first acute exacerbation of interstitial pneumonia
Time to first acute exacerbation of interstitial pneumonia or death, incidence rate
Time to treatment failure: decline from baseline by >=10% relative to %FVC, or decline by >=15% relative to %DLco, or occurrence of death or acute exacerbation

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who are 20 years of age or older at the time of obtaining consent.
2) Patients who are not receiving any treatment for interstitial lung disease, such as antifibrotic agents, immunosuppressive agents, or steroids..
3) Patients diagnosed with idiopathic non-specific interstitial pneumonia (iNSIP), unclassifiable idiopathic interstitial pneumonia, fibrotic hypersensitivity pneumonitis, or rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and meeting the following progressive criteria within 12 months of observation period (since the test that was the starting point for the diagnosis of PPF) prior to enrollment.
Progressive pulmonary fibrosis (PPF) in this study must meet at least 2 of the following 3 criteria, including ii)
i) Worsening of respiratory symptoms
ii) A decline in lung function as measured by at least 5% (relative change) of %FVC or 15% (relative change) of %DLco corrected for Hb concentration.
iii) An increase in fibrotic changes on chest imaging
4) Patients with pulmonary fibrosis exceeding at least 10% of the total lung field on HRCT as assessed by the physician in charge on HRCT images (since the test that was the starting point for the diagnosis of PPF). Fibrosis of the lungs is defined as including reticular shadows or traction bronchiectasis, with or without honeycomb lung findings.
5) Patients with %FVC greater than 50%.
6) Patients with a %DLco greater than 30% and less than 80% corrected for hemoglobin (Hb) concentration
7) Patients with rheumatoid arthritis who have stable symptoms (no new treatment for rheumatoid arthritis must have been started or stopped within 6 weeks prior to enrollment)
8) Patients with rheumatoid arthritis who have not used steroids or immunosuppressive drugs (tacrolimus, mizoribine, methotrexate, leflunomide, etc.), biologics (infliximab, etanercept, adalimumab, golimumab, tocilizumab, abatacept, etc.) or JAK inhibitors (tofacitinib, baricitinib, etc.) for articular manifestations.
However, patients who have used them in the past but not within 12 weeks prior to enrollment may be enrolled.
Immunomodulators (e.g., salazosulfapyridine, busiramine, iguratimod) are allowed.
9) Patients with AST and ALT levels below 100 IU/L and not Child Pugh B,C (the most recent data within 14 days from the date of registration will be used for registration. (The same day of the week 14 days prior is acceptable, based on the date of registration).
10) Creatinine clearance (measured or estimated by Cockcroft-Gault formula):>=30 ml/min (data within 14 days from the date of registration, the most recent data will be used for registration. The same day of the week 14 days prior is acceptable) based on the date of registration.
11) Written consent has been obtained from the patient himself/herself after a thorough explanation of the study content has been given prior to enrollment in the study.

Exclude criteria

1) Patients diagnosed with IPF, COP, AIP, DIP, RB-ILD, LIP and PPFE
2) Patients with interstitial lung disease associated with collagen diseases except rheumatoid arthritis (including cases of overlap syndrome (e.g., Sjogren's syndrome in rheumatoid arthritis patients)) and interstitial lung disease with causes other than fibrotic hypersensitivity pneumonitis
3) Patients already receiving steroids, immunosuppressants (tacrolimus, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil,etc.), or antifibrotic agents at the time of enrollment
4) Patients with a history of acute exacerbation of interstitial lung disease
5) Patients with poorly controlled diabetes mellitus
(>=HbA1c 8.0%)
6) Patients with predominant airflow obstruction (FEV1/FVC less than 0.7 within 30 days prior to enrollment)
7) Patients with complications of acute and chronic systemic infections (e.g., non-tuberculous mycobacterial infections)
8) Patients with acute and chronic pancreatitis
9) Patients with a history of or complications of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV) within 180 days prior to enrollment.
(Patients with a history of these diseases more than 180 days ago may be enrolled if they currently have cardiac function within normal limits and are free of cardiac disease-related symptoms.)
10)Patients with a history of severe pulmonary hypertension (WHO pulmonary hypertension functional classification (WHO-PH) class III or IV)
11) Patients at risk of bleeding
(e.g., genetic predisposition to bleeding, a need for fibrinolytic drugs, therapeutic doses of anticoagulants, or a need for high-dose antiplatelet therapy)
12) Patients with a history of venous thromboembolism (deep vein thrombosis, pulmonary thromboembolism, etc.) or complications.
13) Patients with active malignancy requiring chemotherapy
(Patients who have undergone surgical treatment may be enrolled if there has been no recurrence for at least 1 year)
14) Patients with clinically problematic psychiatric disorders that would preclude enrollment in the study.
15) Pregnant women, lactating women, women who may be currently pregnant, and men and women who are not willing to use contraception during the treatment period.
16) Other patients deemed inappropriate by the physician in charge.

Related Information

• Primary Sponsor: Okamoto Isamu
• Source(s) of Monetary Support: Kakihara Science and Technology Research Foundation