EU-IPFF committed to promoting research in Pulmonary Fibrosis

Interstitial Lung Disease Exacerbations Study

Study Purpose

Interstitial lung disease (ILD) is an umbrella term covering numerous conditions that affect the lung tissue, interfering with the ability of the lungs to take up oxygen. Most ILDs get worse gradually, but sometimes patients can experience a sudden worsening in their symptoms called an acute exacerbation (AE-ILD). Most studies in this area have been done in AEs of idiopathic pulmonary fibrosis (AE-IPF), as IPF is the commonest form of ILD. AE-IPF has very poor outcomes, however AEs of other ILDs are less well studied. Furthermore, there is currently no treatment guideline or established standard of care for the management of patients with AE-fILD. The aim of this research project is to gain a better understanding of AE-ILD in a real-world population. By looking at the clinical records of patients with AE-ILD, the study aims to describe the patient population that gets AE-ILD and how these patients are treated in the "real world" setting. The study will also gather information on patient characteristics such as type of ILD and test results at the time of AE-ILD, and see if any of these factors are associated with better/ worse outcomes in AE-ILD. Finally, the study will collect data on the treatment approaches taken, including both medical therapy such as steroid treatment, as well as specialist care team input. This data on treatment will be used to identify associations between individual treatments and outcomes, as well as to evaluate the NHS services being provided to patients with AE-ILD. Overall, this study will enhance understanding of AE-ILD. This study will provide information to help design clinical trials to test treatments for AE-ILD, to help us create evidence-based clinical guidelines for AE-ILD, and improve the management of patients with AE-ILD.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

• Patients admitted to an acute NHS trust during study period 1st September 2022-31st August 2023 with an underlying or new diagnosis of an ILD (defined by ICD-10 codes) with a fibrotic phenotype (established fibrosis on current or previous radiological imaging) AND.• 1 month or less of worsening of respiratory symptoms.AND.

- Radiological findings (CXR or CT) consistent with acute exacerbation.

- CXR: new bilateral shadowing or infiltrates not seen on previous chest x ray from >1 month prior.

- CT: new bilateral ground glass opacities with or without consolidation.

Exclusion Criteria:

- Pre-existing diagnosis of ILD without fibrosis.

- Absence of radiological evidence of AE-ILD (no new opacities on CXR or CT thorax) - Radiological or clinical features suggestive of other primary diagnosis as determined by treating team, as evidenced by diagnosis on discharge summary.

- Congestive cardiac failure or fluid overload as main discharge diagnosis.

- Lobar pneumonia without other evidence of acute exacerbation of fILD.

- Segmental or larger pulmonary embolus as main discharge diagnosis in absence of acute exacerbation features on imaging.

- Pleural effusion as main discharge diagnosis.

- Pneumothorax as main discharge diagnosis in absence of acute exacerbation features on imaging.

- Acute pneumonitis or acute presentations of interstitial lung disease without evidence of fibrosis (Table 2) - Participant signatory to NHS National Data Opt Out.

- Elective/non-emergency admission.

- Admission under non-medical specialty (except for patients subsequently transferred to care of medical team for treatment of AE-fILD) - In cases where there are >=1 eligible admissions only the first (index) admission shall be included

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06685874
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Royal Devon and Exeter NHS Foundation Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Michael Gibbons, MBChB
Principal Investigator Affiliation	Royal Devon and University healthcare trust
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Interstitial Lung Disease (ILD), Pulmonary Fibrosis

Additional Details

Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (PF-ILDs) are increasingly common fatal disorders with a median life expectancy from diagnosis of 3-5 years. Fibrotic interstitial lung disease (fILD) is a general term for a group of conditions that involve scarring of the lung (fibrosis) with or without evidence of inflammation. While different ILDs are associated with different aetiological factors and disease courses, there is considerable overlap in the characteristics of these conditions. In general, fILDs usually progress in terms of symptoms, lung function, and radiological features, resulting in increasing symptoms and respiratory failure. In addition to the gradual progression that is typical of fILD, these conditions can become acutely worse during episodes of acute exacerbation (AE-fILD). An AE can be defined as an acute (less than one month) deterioration in symptoms associated with new ground glass changes on CT chest and not explained by other pathology such as pulmonary embolus, pneumothorax, or cardiac failure (adapted from the definition by Collard et al for AE-IPF). The prognosis of acute exacerbations of idiopathic pulmonary fibrosis (IPF), the commonest form of fILD, is very poor (over 90% in-hospital mortality in some reports). However, there has been very little research on AEs in non-IPF fILD. Furthermore, there is currently no treatment guideline or established standard of care for the management of patients with AE-fILD. Other significant gaps in the literature in this area, include:

- What is the typical clinical course and outcome of acute exacerbations in non-IPF fILD? - What features predict the risk of in-hospital and post-discharge mortality from AE-fILD (e.g. age, sex, baseline diagnosis)? - Are currently used treatments for AE-fILD effective? How should AE-fILD be managed (steroids, oxygen therapy etc)? - How well are aspects of care that patients find important (e.g. provision of specialist palliative care, opportunities to discuss advanced care planning, and oxygen therapy) delivered to patients with AE-fILD? There are significant gaps in the literature in the field of AE-fILD.

Much of the current practice in AE-fILD management is based on clinical judgement, and adequately powered randomised controlled trials to identify appropriate treatment approaches have not been performed. This has led to significant heterogeneity in the approach to AE-fILD between clinicians and centres, an issue illustrated by the fact that only one of seven NHS trusts in the East Midlands has a treatment guideline specific for the management of AE-fILD (unpublished data). This lack of consistency in approach poses a significant challenge to the design of randomised control trials, as heterogeneity within a standard care control arm can obscure any specific signals. Furthermore, in the absence of RCTs, there is the potential that clinicians may unintentionally use interventions that are harmful. The study is an observational cohort study of patients admitted to hospital with AE-fILD to answer the questions listed above. These data will help to clarify research priorities in this area, and identify areas where care could improve and allow us to make recommendations for clinical care. The study will also use these data to inform and generate hypotheses for future clinical trials.

Arms & Interventions