Immunosuppressant Combined With Pirfenidone in CTD-ILD

Efficacy, Safety and Predictive Indicators of Immunosuppressant Combined With Pirfenidone in the Treatment of Connective Tissue Disease-related Interstitial Lung Disease (CTD-ILD)

A prospective cohort study was used to observe the efficacy and safety of different immunosuppressive agents with/wo pirfenidone on CTD-ILD patients in Qilu Hospital of Shandong University for 36 months.The main research endpoints are lung function, patient dyspnea score, 6-minute walking distance, imaging indicators, primary disease activity, adverse reactions, etc.

Study Overview

• Status: Active, not recruiting
• Conditions: Connective Tissue Diseases; Interstitial Lung Disease; Pirfenidone
• Intervention / Treatment: Drug: Pirfenidone; Drug: DMARDs

Detailed Description

This study will enroll 200 cases of connective tissue disease-related interstitial lung disease (CTD-ILD) patients in China, including inflammatory myopathy (IIM) patients, rheumatoid arthritis (RA) patients, systemic sclerosis (SSc) patients, Sjogren's syndrome (SS) patients and other connective tissue disease patients.According to the patient's condition,the participants plan to be treated with different immunosuppressive agents with/wo pirfenidone .Participants can choose to continue the study up to 36 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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jiaqi Wang; Phone Number: 0086-0531-82169654; Email: 1940273314@qq.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who meet the following inclusion criteria will be eligible to participate in the study:

  1. Aged 18-80 years;
  2. In accordance with the diagnostic criteria of connective tissue disease-related pulmonary interstitial disease (CTD-ILD);The diagnosis of CTD is in line with the international classification standard of rheumatism (including inflammatory myopathy, systemic sclerosis, rheumatoid arthritis, sjogren's syndrome, systemic lupus erythematosus, mixed connective tissue disease, undifferentiated connective tissue disease);
  3. Subjects are willing to participate and use medication and follow-up time according to the treatment plan, and sign the informed consent;

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from the study:

  1. Subjects have non-diffuse connective tissue disease or other arthritis other than RA, such as ANCA-relateed vasculitis, psoriatic arthritis, etc;
  2. Patients who have ILD with clear etiology, such as HIV, GVHD ；

  3. Combined viscera function significantly abnormal patient:

     1. Liver: AST, ALT >1.3ULN; Bilirubin >1.5 ULN; or previous diagnosis of viral hepatitis;
     2. Kidney: Creatinine clearance <30 mL/min;
     3. Lung: Airway obstruction (pre-bronchodilator FEV1/FVC <0.7); pleural effusion accounts for more than 20% of pleural effusion ;severe pulmonary infection or other clinically significant pulmonary abnormalities;
     4. Cardiovascular: Myocardial infarction or unstable angina within six months;
     5. Gastrointestinal tract: With active peptic ulcer or bleeding;
     6. Blood system: Severe anemia, decreased white blood cells and platelets
     7. Nervous system: Patients with mental disorders; cerebral thrombosis events within the past 1 year;
  4. Combined with poor prognosis of diseases, such as cancer, genetic diseases and so on;
  5. Women during pregnancy or lactation or childbearing age cannot ensure effective contraception;
  6. According to the researchers, exhibited evidence of alcohol or drug abuse;
  7. Any other major medical events beyond control;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pirfenidone group; CTD-ILD patients treated with DMARDs and pirfenidone	Drug: Pirfenidone; CTD-ILD patients treated with pirfenidone up to the maximum tolerable dose; Drug: DMARDs; CTD-ILD patients treated with DMARDs according to the condition of the disease
Active Comparator: No-Pirfenidone group; CTD-ILD patients treated with DMARDs, without pirfenidone	Drug: DMARDs; CTD-ILD patients treated with DMARDs according to the condition of the disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FVC	Change in forced vital capacity(FVC) from 12 months to baseline	12 months
Change in DLCo	Change in carbon monoxide diffusing capacity (DLCo) from 12 months to baseline	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in FVC	Changes from baseline in forced vital capacity(FVC)	6 months，24 months，36 months
Changes in DLCo	Changes from baseline in carbon monoxide diffusing capacity (DLCo)	6 months，24 months，36 months
Changes from baseline in Dyspnea score	Changes from baseline in Dyspnea score. Dyspnea score:activity tolerance of patients with dyspnea in daily life: 0: normal, 1: dyspnea when climbing the fifth floor, 2: dyspnea when climbing the third floor, 3: dyspnea when climbing the second floor, 4: Difficulty in breathing when walking on the flat ground 100-500m, 5: Difficulty in breathing when walking on flat ground for 50-100m, 6: Difficulty in breathing when walking on flat ground for 15-50m, 7: Difficulty in breathing when walking on flat ground 5-15m, 8: Difficulty in breathing during daily dressing, 9: Difficulty in breathing when eating, 10: Difficulty in breathing when resting.The higher the score, the more severe the disease.	6 months，12 months, 24 months，36 months
Imaging changes	Changes from baseline in high-resolution computed tomography (HRCT)	6 months，12 months, 24 months，36 months
Changes from baseline in 6 minutes walking distance	Changes from baseline in 6 minutes walking distance	6 months，12 months, 24 months，36 months
Changes from baseline in C-reactive protein(CRP)	Changes from baseline in C-reactive protein(CRP)	6 months，12 months, 24 months，36 months
Changes from baseline in Erythrocyte Sedimentation Rate(ESR)	Changes from baseline in Erythrocyte Sedimentation Rate(ESR)	6 months，12 months, 24 months，36 months
Changes from baseline in VAS score	The visual analogue scale (VAS) is used for pain assessment. The basic method is to use a moving ruler with a length of about 10cm. One side is marked with 10 scales. The two ends are respectively "0" and "10" points. A point of 0 means no pain, and a point of 10 means the most unbearable. Severe pain. It can reflect the degree of activity of the primary disease.	6 months，12 months, 24 months，36 months
Number of participants with "adverse events (AEs)"	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.	Up to month 36

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Principal Investigator: Yang Xiaoyun, Dr., Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 9, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; interstitial lung disease; systemic sclerosis; connective tissue disease; pirfenidone; inflammatory myopathy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Connective Tissue Diseases; Lung Diseases, Interstitial; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: CTD-ILD QiluH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No