Efficacy and Immune Function of Pirfenidone in CTD-ILD

Sponsor

Qilu Hospital of Shandong University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05505409

Collaborator

(none)

120

Enrollment

Location

Arms

43.3

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A single-center randomized controlled study was used to observe the efficacy and immune function with/wo pirfenidone on CTD-ILD patients in QIlu Hospital of Shanndong University for 24 months. The main research endpoints are lung function ,patient dyspnea score,imaging indicators and so on.

Condition or Disease	Intervention/Treatment	Phase
Pirfenidone Connective Tissue Diseases Interstitial Lung Disease	Drug: Pirfenidone Drug: glucocorticoid and immunosuppressant	Phase 4

Detailed Description

This study will enroll 120 cases of connetive tissue disease-related interstitial lung disease (CTD-ILD)patients in China ,including inflammatory myopathy(IIM)patients,Rheumatoid arthritis (RA)patients,systemic sclerosis(ssc)patientsand other connective tissue disease patients.This study will observe the effect of combine or not combined with pirfenidone treatment on lung function and oral mucosal mircoflora of different types of CTD-ILD ,the optimal dose and blood concentration of pirfenidone in combination with glucocorticoid and immunosuppressant ,as well as the screening and prediction effects of related biomarkers .Participants can choose to continue the study up to 24 months.The efficacy and safety of the treatment in CTD-ILD patients will be evaluated with lung function,quality of life / cardiopulmonary function assessment and other disease activity indices.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 22, 2022

Anticipated Primary Completion Date :

Jul 30, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pirfenidone group CTD-ILD patients treated with pirfenidone、glucocorticoid and immunosuppressant.	Drug: Pirfenidone Drug:pirfenidone CTD-ILD patients treated with pirfenidone up to the maximum tolerable dose Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease Other Names: glucocorticoid and immunosuppressant Drug: glucocorticoid and immunosuppressant Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease
Active Comparator: No-pirfenidone group CTD-ILD patients treated withglucocorticoid and immunosuppressant,without pirfebidone	Drug: glucocorticoid and immunosuppressant Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease

Arm

Intervention/Treatment

Experimental: pirfenidone group

CTD-ILD patients treated with pirfenidone、glucocorticoid and immunosuppressant.

Drug: Pirfenidone

Drug:pirfenidone CTD-ILD patients treated with pirfenidone up to the maximum tolerable dose Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease

Other Names:

glucocorticoid and immunosuppressant

Drug: glucocorticoid and immunosuppressant

Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease

Active Comparator: No-pirfenidone group

CTD-ILD patients treated withglucocorticoid and immunosuppressant,without pirfebidone

Drug: glucocorticoid and immunosuppressant

Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease

Outcome Measures

Primary Outcome Measures

Change in FVC [6 months]
change in forced vital capacity(FVC) from 6 months to baseline

Secondary Outcome Measures

Change in FVC [3months 12 months 24 months]
change from baseline in forced vital capacity (FVC)
change in FEV1%、DLco%、TLC% [3months 6months 12months 24months]
change from baseline in carbon monoxide diffusing capacity (DLco)、FEV1、TLC
change in DLCO% [6months 12months 24months]
Percentage of patients and time with DLco% decreased>15% compared to baseline
change in FVC [6months 12months 24months]
Percentage of patients and time with FVC% decreased>10% compared to baseline
Progression-free survival [24months]
survival with a predicated absolute FVC% decrease of no more than 10% from baseline,and a predicated absolute DLco% decrease of no more than 15% from baseline
change in FVC and DLco [6months 12months 24months]
absolute value change of FVC(ml) and DLco(ml) at each time point and annual decline rate compared with baseline
changes from baseline in 6 minutes walking distance [6months]
changes from baseline in 6 minutes walking distance
change in pulse oxygen saturation [6months]
the worst oxygen saturation as measured by pulse oxygen saturation(SpO2) was observed during 6 minutes walking distance
Imaging changes [6months 12months 24months]
changes from baseline in high-resolution computed tomography (HRCT)
changes in St. George's Respiratory Questionnaire(SGRQ) score [6months 12months 24months]
changes in St. George's Respiratory Questionnaire(SGRQ) score at each time point from baseline ;K-BILdD3 questionnaire scoring
changes in the mMRC dyspnea score [6months 12months 24months]
changes in the mMRC dyspnea score at each time point compared to baseline
clinical deteriorration [24months]
The time and incidence of the first clinical deterioration ,Number of clinical exacerbations,Time between the all-cause deaths
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators. [6months 12months 24months]
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators.
Changes from baseline in primary disease activity [24months]
Changes from baseline in primary disease activity
Adverse events , timing,type,extent,frequency,and outcome of SAE [24months]
Adverse events , timing,type,extent,frequency,and outcome of SAE
FVC% area under the curve [6months 12months 24months]
forced vital capacity (FVC)% area under the curve
Predicators of pirfenidone response in each disease subgroup [6months 12months 24months]
Predicators of pirfenidone response in each disease subgroup

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be at least 18 years old ;
Conform to several diagnostic criteria of CTD(RA,IIM,SSc) and UCTD/IPAF classification criteria;
HRCT diagnosis was confirmed to be interstitial lung disease (ILD) with corresponding clinical manifestations;
Patients who can complete vital capacity (FVC) or carbon monoxide dispersion(DLco) test (using Hb correction);
ILD patients with clinical deterioration more than 1 month after diagnosis, or poor response or intolerance after previous GC and IS treatment, or poor response or intolerance to other anti-fibrosis drugs (for acetylhemioptic acid, nidanib, etc.), or effective previous use of PFD, clinical symptoms or ILD index aggravation after drug withdrawal for more than 3 months
If concomitant therapy with IS 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, Elamud, etc.
Concomitant hormones: IIM patients with hormone dose (calculated as prednisone equivalent dose) ≤60mg/d and relatively stable disease; For other CTD patients, the hormone dose (calculated as prednisone equivalent dose) was ≤40mg/ day for at least 1 month

Exclusion Criteria:

Subjects had systemic vasculitis, arthritis other than CTD or RA, such AS psoriatic arthritis, SPA, AS, SLE, and pSS;
ILD patients with other obvious causes, such as HIV, GVHD, etc.;
Patients with obvious organ dysfunction;

(1) Liver :AST, ALT, R-GT, bilirubin at 1.5 ULN, or previously diagnosed with viral hepatitis; (2) Kidney: creatinine clearance rate was 30ml /min; (3) Lung: airway obstruction (pre-bronchodilator FEV1/FVC LT; 0.7), pleural effusion accounts for more than 20% of pleural effusion, severe lung infection or other clinically significant lung abnormalities; (4) Cardiovascular disease: 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 thrombosis events (stroke and transient ischemic attack) within the last 1 year; 4. Diseases with poor prognosis, such as tuberculosis, cancer and genetic diseases; 5. Effective contraception cannot be guaranteed during pregnancy, lactation or childbearing age; 6. Evidence of alcohol or drug abuse, according to the researcher; 7. Allergic to glucocorticoids, immunosuppressants and PFD; 8. Patients who cannot complete regular follow-up and post-treatment lung function test; 9. Patients using PFD who were not included in the efficacy analysis but included in the safety analysis: those who had been using PFD for less than 3 months 6 months prior to the primary endpoint; The duration of use was less than 3 months and the total duration of use was less than 6 months before the 24th month of study end.