Patients aged ≥18 years will be eligible for the trial if they have a physician-diagnosed fibrosing ILD, such as connective tissue disease (CTD)-associated ILD, chronic fibrosing hypersensitivity pneumonitis (HP), idiopathic non-specific interstitial pneumonia (iNSIP), unclassifiable idiopathic interstitial pneumonia (IIP), environmental/occupational lung disease or sarcoidosis, present with features of diffuse fibrosing lung disease of >10% extent on HRCT and meet the protocol criteria for progression within 24 months of screening, as assessed by the investigator. The criteria for evidence of progression are worsening lung function (clinically significant, ≥10% relative decline in forced vital capacity (FVC)) or worsening lung function (≥5–<10% relative decline in FVC) together with worsening respiratory symptoms and/or evidence of increasing fibrosis on chest imaging, despite treatment with unapproved medications used in clinical practice to treat ILD. A full list of the criteria for progression is provided in online supplementary table S1 .
At screening, the most recent HRCT image (taken within the previous 12 months) will be evaluated by central review according to the protocol to ensure that relevant lung fibrosis is present. In addition, the HRCT pattern will be determined for randomisation stratification. This review will be performed by two independent specialists in thoracic radiology with extensive expertise in the interpretation of HRCT of the chest. The reviewers will be blinded to patients’ demographic and clinical data.
In addition, eligible patients will have a FVC>45% of predicted value and a diffusing capacity of the lungs for carbon monoxide (DLCO) of >30% and <80% of predicted at randomisation.
As nintedanib is already approved for patients with IPF, patients will be excluded if they meet diagnostic criteria for IPF according to the ATS/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association 2011 guidelines.13 (link) Patients with contraindications to nintedanib, as labelled, will also be excluded. Other exclusion criteria include treatment at baseline with any of the following drugs: azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, mycophenolate mofetil or oral corticosteroids (>20 mg/day). Patients who require use of these medications to control an underlying disease such as CTD will not be considered for participation in the study. In case of worsening of PF-ILD and/or worsening of the underlying CTD during the treatment period, the use of any of these drugs will be allowed after 6 months of study treatment, if judged necessary by the investigator.
A full list of inclusion and exclusion criteria is given in onlinesupplementary table S1 .
At screening, the most recent HRCT image (taken within the previous 12 months) will be evaluated by central review according to the protocol to ensure that relevant lung fibrosis is present. In addition, the HRCT pattern will be determined for randomisation stratification. This review will be performed by two independent specialists in thoracic radiology with extensive expertise in the interpretation of HRCT of the chest. The reviewers will be blinded to patients’ demographic and clinical data.
In addition, eligible patients will have a FVC>45% of predicted value and a diffusing capacity of the lungs for carbon monoxide (DLCO) of >30% and <80% of predicted at randomisation.
As nintedanib is already approved for patients with IPF, patients will be excluded if they meet diagnostic criteria for IPF according to the ATS/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association 2011 guidelines.13 (link) Patients with contraindications to nintedanib, as labelled, will also be excluded. Other exclusion criteria include treatment at baseline with any of the following drugs: azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, mycophenolate mofetil or oral corticosteroids (>20 mg/day). Patients who require use of these medications to control an underlying disease such as CTD will not be considered for participation in the study. In case of worsening of PF-ILD and/or worsening of the underlying CTD during the treatment period, the use of any of these drugs will be allowed after 6 months of study treatment, if judged necessary by the investigator.
A full list of inclusion and exclusion criteria is given in online
