Evaluating the effects of Pirfenidone on lung function in patients with connective tissue disease-related lung issues

Efficacy, Safety, Immune Function of Pirfenidone in the Treatment of Connetive Tissue Disease -Related Interstitial Lung Disease(CTD-LID)

This study is testing if the medication Pirfenidone can improve lung function in people with lung problems caused by connective tissue diseases compared to standard treatments.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Qilu Hospital of Shandong University (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT05505409 on ClinicalTrials.gov

What this trial studies

This clinical trial is a single-center randomized controlled study aimed at assessing the efficacy and safety of Pirfenidone in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) over a period of 24 months. A total of 120 patients will be enrolled and randomly assigned to receive either Pirfenidone or standard treatment with glucocorticoids and immunosuppressants. The primary endpoint is lung function measured by forced vital capacity (FVC) at 6 months, along with evaluations of clinical dyspnea, walking distance, and imaging indicators throughout the study. The trial will also analyze the relationship between Pirfenidone concentration, clinical effects, safety, and immune function.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with CTD-ILD, particularly those with rheumatoid arthritis, systemic sclerosis, or inflammatory myopathy who have not responded well to standard treatments.

Not a fit: Patients who have not been diagnosed with connective tissue diseases or those who are not experiencing significant symptoms of interstitial lung disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve lung function and quality of life for patients suffering from CTD-ILD.

How similar studies have performed: Other studies have shown promising results with Pirfenidone in similar conditions, suggesting potential efficacy in this patient population.

Eligibility criteria

1. Age ≥18 years;
2. Meet several CTD diagnostic criteria (RA, IIM, SSc) and UCTD/IPAF classification criteria;
3. HRCT diagnosis confirmed interstitial lung disease (ILD) with corresponding clinical manifestations;
4. Patients who were able to complete vital capacity (FVC) or carbon monoxide dispersion (DLco) tests (with Hb correction).
5. Patients with clinical deterioration more than 1 month after diagnosis of ILD history, or poor response or intolerance to Glucocorticoids or immunosuppressants treatment, or poor response or intolerance to other antifibrotic drugs (acetyl hemitrine, nidanib, etc.), or effective use of PFD, and exacerbation of clinical symptoms or ILD indicators more than 3 months after withdrawal of the drug.
6. Poor response was defined as no improvement in one of the following:

(1) Symptoms of dyspnea such as cough, chest tightness, breathlessness, shortness of breath after activity, or decreased activity endurance;

(2) the worst decrease in oxygen saturation as measured by pulse oxygen saturation (SpO2) observed during 6MWD;

(3) There was no improvement in pulmonary ventilation (FVC%) or lung dispersion (DLco%);

(4) HRCT findings: new onset, fibrosis tendency or density of ILD lesions were not decreased;

Clinical deterioration was defined as meeting one of three criteria:

1. Clinical deterioration or dyspnea within 4 weeks;
2. New or worsening radiological abnormalities on chest X-ray or high-resolution CT;
3. Objective deterioration of pulmonary function tests or gas exchange, defined as meeting at least one of the following criteria:

1) Start long-term oxygen therapy or increase oxygen supplementation by at least 1 L/min to maintain resting oxygen saturation of at least 90%;

2) FVC decreased by more than 5% compared with the previously measured value; Or a decrease in DLCO of more than 10% from previous measurements; Or a 20% decrease in 6MWD from previous measurements.

7. If concomitant therapy with immunosuppressants was used, the dose was stable for at least 4 weeks before the baseline period. The types of immunomodulator hydroxychloroquine (HCQ) or immunosuppressive agents are MMF, TAC, JAKi, CTX, LEF, AzA, iguratimod etc.

8. Concomitant glucocorticoids: IIM patients with glucocorticoids dose (calculated as the equivalent dose of prednisone) ≤60mg/d and relatively stable disease; For other CTD patients, the glucocorticoids dose (calculated as prednisone equivalent dose) was ≤40mg/ day for at least 1 month.

Exclusion Criteria:

1. Subjects have systemic vasculitis, other arthritis other than CTD or RA such AS psoriatic arthritis, SPA, AS, SLE and pSS;

2. ILD patients with other obvious causes, such as HIV, GVHD, etc.

3. Patients with obvious abnormal combined organ function;

1. Liver :AST, ALT, R-GT, bilirubin at 1.5 ULN, or previously diagnosed viral hepatitis;
2. Kidney: creatinine clearance rate 30ml /min;
3. Lung: airway obstruction (pre-bronchodilator FEV1/FVC \& LT; 0.7), pleural effusion accounted for more than 20% of pleural effusion, severe pulmonary infection or other clinically significant pulmonary abnormalities;
4. Cardiovascular: myocardial infarction within 6 months;
5. gastrointestinal tract: active peptic ulcer or bleeding;
6. Blood system: severe anemia, leukopenia, thrombocytopenia;
7. Nervous system: patients with mental disorders; Cerebral thrombotic events (stroke and transient ischemic attack) within the last 1 year;

4. Tuberculosis, cancer, hereditary diseases and other diseases with poor prognosis;

5. Effective contraception cannot be guaranteed during pregnancy, lactation or childbearing age;

6. Evidence of alcohol or drug abuse, according to the researchers;

7. Allergic to glucocorticoids, immunosuppressants and PFD;

8. Unable to complete regular follow-up and post-treatment pulmonary function tests;

9. PFD users not included in the efficacy analysis but included in the safety analysis: those who had used PFD for less than 3 months 6 months before the primary endpoint; The duration of use was less than 3 months before the 24th month of the syudy and the total duration of use was less than 6 months.

Where this trial is running

Jinan, Shandong

• Qilu Hospital — Jinan, Shandong, China (Recruiting)

Study contacts

• Principal investigator: xiaoyun yang, Dr — Study Principal Investigator Qilu HOspital of Shandong Uniwersity
• Study coordinator: Qiang Shu, Dr

Conditions Pirfenidone; Connective Tissue Diseases; Interstitial Lung Disease; pirfenidone; interstitial lung disease; connective tissue disease; rheumatoid arthritis; systemic sclerosis