The Nintedanib in Progressive Pneumoconiosis Study (NiPPS): a Collaborative NSW Treatment Trial

Study Overview
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Brief Summary
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Prospective clinical pilot study for subjects diagnosed with Occupational Progressive Pneumoconiosis. Subjects will be treated with Nintedanib 150mg twice daily for 3 years.

Detailed Description
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100 Patients with asbestosis, silicosis, coal workers pneumoconiosis and diffuse dust fibrosis will be included. Patients will have an FVC ≥45% predicted (no upper threshold), and a diffusion capacity of the lung for carbon monoxide (TLCO) above 30% predicted. Patients will be randomised to receive Nintedanib 150 mg twice daily, with the dose of the study drug reduced to 100 mg twice daily or interrupted temporarily in the case of adverse events (AEs).The primary end point will be the annual decline in FVC, measured in millilitres per year, calculated from serial measurements over 36 months. Lung function testing will be performed at baseline; 2, 4, 6, 12, 18, 24, 30, 36, 44 and 52 weeks, and every 4 months thereafter until study cessation or withdrawal at a maximum of 36 months. In patients who show clinical benefit as per the end points specified access to Nintedanib treatment will be continued.

Official Title
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The Nintedanib in Progressive Pneumoconiosis Study (NiPPS): a Collaborative NSW Treatment Trial

Conditions
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Pneumoconiosis Coal, Asbestosis, Silicosis

Intervention / Treatment
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* Drug: Nintedanib 150 MG [Ofev]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pneumoconiosis diagnosis confirmed at the Occupational MDT (Occ-MDT) diffuse fibrosing lung disease of extent >10% on HRCT with protocol criteria for progression Asbestosis, silicosis, coal worker's pneumoconiosis and diffuse dust fibrosis FVC ≥45% predicted and TLCO above 30% predicted Exclusion Criteria: idiopathic pulmonary fibrosis (IPF) and non-occupational progressive pulmonary fibrosis ILD due to connective tissues disorders, hypersensitivity pneumonitis, non-occupational interstitial pneumonia, non-occupational sarcoidosis contraindications to Nintedanib (forthcoming surgery, use of anticoagulants, high CVD risk, liver function abnormalities)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective clinical pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Arm<br>Nintedanib 150mg twice daily for 3 years | Drug: Nintedanib 150 MG [Ofev]<br>* Nintedanib 150mg twice daily for 3 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| annual decline in FVC | measured in millilitres per year, calculated from serial measurements | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| K-BILD score | Absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) total score. The KBILD domain and total score ranges are 0-100; 100 represents best health status | week 52 | 
| Time to acute exacerbation | an acute, clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormality, including unexplained worsening or development of dyspnea,new diffuse pulmonary infiltrates visualized on chest radiography, HRCT, or both, or the development of parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the preceding visit; and exclusion of any known causes of acute worsening, including infection, left heart failure, pulmonary embolism, and any identifiable cause of acute lung injury, in accordance with routine clinical practice and microbiologic studies. | 36 months | 
| Time to referral for Lung transplantation | Respiratory deterioration which necessitates a referral for lung transplant | 36 months | 
| Time to death | Respiratory deterioration leading to death | 12, 24 and 36 months |