FIBRotic Interstitial Lung Disease With Nocturnal hypOXaemia and EXercise Induced desaTuRAtion (FIBRINOX-EXTRA)

A Prospective Observational Study Investigating Whether Nocturnal Hypoxaemia and Exercise Induced Desaturation Predict Functional Deterioration in Patients With Fibrotic Interstitial Lung Disease

This is an observational clinical research study investigating patients with fibrotic interstitial lung disease (fILD), also known as pulmonary fibrosis.

It is not known why some patients with fILD clinically deteriorate. This study will investigate whether measuring oxygen levels during sleep or exercise can help identify patients who are at increased risk of clinical deterioration.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Hypertension; Interstitial Lung Disease; Fibrosis Lung
• Intervention / Treatment: Other: Prospective

Detailed Description

This work will build upon the FIBRINOX study, previous clinical research conducted by the Guy's and St Thomas' ILD research team. The FIBRINOX study showed that patients with fILD and normal oxygen saturations at rest, but who desaturate whilst asleep or during exercise, have a significantly increased mortality and greater reduction in quality of life compared to patients who do not desaturate at night or during exercise.

The reasons for these differences in mortality and health related quality of life are not known. Data suggests that worsening fILD and the development of pulmonary hypertension, a condition characterised by increased pressure in the pulmonary arteries that is associated with poorer outcomes, may be playing a role.

This clinical research study will recruit approximately 160 patients with a tertiary ILD centre diagnosis of fibrotic interstitial lung disease (fILD). Data from routinely performed investigations as part of tertiary ILD assessment will be systematically recorded.

Investigations will include lung function tests, echocardiography, blood tests, a 6-minute walk test and overnight oximetry. Participants will also complete several quality-of-life questionnaires. These investigations will be performed at baseline, and again at 12 months, with all tests also repeated at 6 months except for an echocardiogram. After the initial 1 year study period, a 3 year post-recruitment mortality and right heart catheter check will be performed using the participants' medical records. Data will be collected from CT scans and right heart catheters if performed during the study period as part of the participants usual clinical care.

This study is designed to establish whether patients with fILD who desaturate during sleep or exercise are more likely to experience functional decline, as well as confirm previous findings of increased mortality and worsening quality of life as demonstrated in the FIBRINOX study. The data generated by this observational study will help generate future hypotheses, research questions and clinical study.

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Alexandra Lawrence, MBBS; Phone Number: 58207 02071887188; Email: alexandra.lawrence@gstt.nhs.uk
• Study Contact Backup: Name: Gillian Radcliffe, BSc; Phone Number: 88070 07395285492; Email: gillian.radcliffe@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's & St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a tertiary ILD centre diagnosis of fibrotic interstitial lung disease

Description

Inclusion Criteria:

1. Patients aged 18 year and over
2. Tertiary MDT diagnosis of FILD with >10% fibrosis on CT chest as determined by the investigator. Underlying diagnoses to include but not limited to: idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonitis (NSIP), chronic hypersensitivity pneumonitis (CHP), connective tissue disease-related interstitial lung disease (CTD-ILD), fibrotic organising pneumonia (FOP) and pulmonary sarcoidosis.
3. Able to provide informed written consent

Exclusion Criteria:

1. The use of or any indication for long-term oxygen therapy (LTOT)
2. Known moderate or severe obstructive sleep apnoea with an apnoea/hypopnoea index (AHI) or oxygen desaturation index (ODI) over 15 events per hour
3. Radiological predominance of emphysema compared with fibrosis on CT chest
4. Inability to complete all health status questionnaires as set out in this protocol, with appropriate support
5. A confirmed diagnosis of pulmonary hypertension
6. Significant cardiovascular comorbidity including severe, uncontrolled hypertension, uncontrolled arrhythmia, recent acute coronary syndrome within 30 days prior to study enrolment, that could mean exercise testing poses a risk to patient health, in the opinion of the investigator
7. Musculoskeletal comorbidity that will preclude the participant's ability to reliably complete the complete 6-minute walk test (6MWT)
8. Participation in another research project which may confound this study's research findings

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Retrospective; All participants will be in one group which is the collection of retrospective data	Other: Prospective; Collection of prospective data all ready available for participant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute walk distance	As measured by 6-minute walk test	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	If death occurs during the study period, and the cause of death	52 and 156 weeks
Clinical deterioration	Defined by: decline in forced vital capacity (FVC) >10% or death	52 weeks
Decline in FVC	Decline in forced vital capacity	52 weeks
Decline in TLCO	Decline in total diffusing capacity of the lungs for carbon monoxide	52 weeks
Pulmonary hypertension	Right heart catheter confirmed pulmonary hypertension	52 and 156 weeks
Change in arterialised capillary blood gas pO2	Arterialised capillary blood gas partial pressure of oxygen	52 weeks
Change in arterialised capillary blood gas oxygen saturations	Arterialised capillary blood gas oxygen saturations	52 weeks
Change in arterialised capillary blood gas pCO2	Arterialised capillary blood gas partial pressure of carbon dioxide	52 weeks
Change in arterialised capillary blood gas HCO3	Arterialised capillary blood gas partial pressure of bicarbonate	52 weeks
Change in arterialised capillary blood gas pH	Arterialised capillary blood gas pH	52 weeks
Time to first acute exacerbation of fILD	The number of days until the participant requires hospital admission for an acute worsening of their respiratory condition, not attributable to other causes	52 weeks
Rate of acute exacerbation of fILD	The number of times the participant requires hospital admission for an acute worsening of their respiratory condition, not attributable to other causes	52 weeks
Change in NT-proBNP/BNP level	Change in NT-proBNP/BNP level from baseline	52 weeks
Change in troponin level	Change in troponin level from baseline	52 weeks
Change in peak TRV	Change in peak tricuspid regurgitation velocity (TRV)	52 weeks
Change in cardiac chamber size/area	Change in cardiac chamber size/area	52 weeks
Change in cardiac chamber area	Change in cardiac chamber area	52 weeks
Change in RV/LV basal diameter area ratio	Change in right ventricle to left ventricle basal diameter area ratio	52 weeks
Change in MPA:AA diameter ratio	Change in main pulmonary artery to ascending aorta diameter ratio	52 weeks
Change in TAPSE/sPAP ratio	Change in tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio	52 weeks
Change in European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire score	Change in score of European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire	52 weeks
Change in King's Brief Interstitial Lung Disease (KBILD) questionnaire score	Change in score of King's Brief Interstitial Lung Disease (KBILD) questionnaire	52 weeks
Change in Living with Pulmonary Fibrosis (L-IPF) questionnaire score	Change in score of Living with Pulmonary Fibrosis (L-IPF) questionnaire	52 weeks

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: Boehringer Ingelheim
• Investigators: Principal Investigator: Alex West, MBBS, Guys and St. Thomas NHS Foundation Hospital

Publications and helpful links

General Publications

• Myall KJ, West AG, Martinovic JL, Lam JL, Roque D, Wu Z, Maher TM, Molyneaux PL, Suh ES, Kent BD. Nocturnal Hypoxemia Associates With Symptom Progression and Mortality in Patients With Progressive Fibrotic Interstitial Lung Disease. Chest. 2023 Nov;164(5):1232-1242. doi: 10.1016/j.chest.2023.05.013. Epub 2023 May 13.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Fibrosis; Hypertension; Lung Diseases; Pulmonary Fibrosis; Hypertension, Pulmonary; Lung Diseases, Interstitial; Hypoxia
• Other Study ID Numbers: 329843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared or made available to researchers outside of the site research team where the patient is based, and GSTT ILD research team.

Drug and device information, study documents

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