## Protocol Section
### Identification Module
**NCT ID:** NCT06416163

**Acronym:** FIBRINOX-EXTRA

**Brief Title:** FIBRotic Interstitial Lung Disease With Nocturnal hypOXaemia and EXercise Induced desaTuRAtion

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

#### Organization Study ID Info
**ID:** 329843
#### Organization
**Class:** OTHER
**Full Name:** Guy's and St Thomas' NHS Foundation Trust
### Status Module
#### Completion Date
**Date:** 2029-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-10-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-01-19
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Boehringer Ingelheim

#### Lead Sponsor

**Class:** OTHER

**Name:** Guy's and St Thomas' NHS Foundation Trust

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Interstitial Lung Disease

- Fibrosis Lung

- Pulmonary Hypertension

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** All participants will be in one group which is the collection of retrospective data

**Intervention Names:**

- Other: Prospective

**Label:** Retrospective

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Retrospective

**Description:** Collection of prospective data all ready available for participant

**Name:** Prospective

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** As measured by 6-minute walk test

**Measure:** Change in 6-minute walk distance

**Time Frame:** 52 weeks

#### Secondary Outcomes

**Description:** If death occurs during the study period, and the cause of death

**Measure:** Mortality

**Time Frame:** 52 and 156 weeks

**Description:** Defined by: decline in forced vital capacity (FVC) \>10% or death

**Measure:** Clinical deterioration

**Time Frame:** 52 weeks

**Description:** Decline in forced vital capacity

**Measure:** Decline in FVC

**Time Frame:** 52 weeks

**Description:** Decline in total diffusing capacity of the lungs for carbon monoxide

**Measure:** Decline in TLCO

**Time Frame:** 52 weeks

**Description:** Right heart catheter confirmed pulmonary hypertension

**Measure:** Pulmonary hypertension

**Time Frame:** 52 and 156 weeks

**Description:** Arterialised capillary blood gas partial pressure of oxygen

**Measure:** Change in arterialised capillary blood gas pO2

**Time Frame:** 52 weeks

**Description:** Arterialised capillary blood gas oxygen saturations

**Measure:** Change in arterialised capillary blood gas oxygen saturations

**Time Frame:** 52 weeks

**Description:** Arterialised capillary blood gas partial pressure of carbon dioxide

**Measure:** Change in arterialised capillary blood gas pCO2

**Time Frame:** 52 weeks

**Description:** Arterialised capillary blood gas partial pressure of bicarbonate

**Measure:** Change in arterialised capillary blood gas HCO3

**Time Frame:** 52 weeks

**Description:** Arterialised capillary blood gas pH

**Measure:** Change in arterialised capillary blood gas pH

**Time Frame:** 52 weeks

**Description:** The number of days until the participant requires hospital admission for an acute worsening of their respiratory condition, not attributable to other causes

**Measure:** Time to first acute exacerbation of fILD

**Time Frame:** 52 weeks

**Description:** The number of times the participant requires hospital admission for an acute worsening of their respiratory condition, not attributable to other causes

**Measure:** Rate of acute exacerbation of fILD

**Time Frame:** 52 weeks

**Description:** Change in NT-proBNP/BNP level from baseline

**Measure:** Change in NT-proBNP/BNP level

**Time Frame:** 52 weeks

**Description:** Change in troponin level from baseline

**Measure:** Change in troponin level

**Time Frame:** 52 weeks

**Description:** Change in peak tricuspid regurgitation velocity (TRV)

**Measure:** Change in peak TRV

**Time Frame:** 52 weeks

**Description:** Change in cardiac chamber size/area

**Measure:** Change in cardiac chamber size/area

**Time Frame:** 52 weeks

**Description:** Change in cardiac chamber area

**Measure:** Change in cardiac chamber area

**Time Frame:** 52 weeks

**Description:** Change in right ventricle to left ventricle basal diameter area ratio

**Measure:** Change in RV/LV basal diameter area ratio

**Time Frame:** 52 weeks

**Description:** Change in main pulmonary artery to ascending aorta diameter ratio

**Measure:** Change in MPA:AA diameter ratio

**Time Frame:** 52 weeks

**Description:** Change in tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio

**Measure:** Change in TAPSE/sPAP ratio

**Time Frame:** 52 weeks

**Description:** Change in score of European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire

**Measure:** Change in European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire score

**Time Frame:** 52 weeks

**Description:** Change in score of King's Brief Interstitial Lung Disease (KBILD) questionnaire

**Measure:** Change in King's Brief Interstitial Lung Disease (KBILD) questionnaire score

**Time Frame:** 52 weeks

**Description:** Change in score of Living with Pulmonary Fibrosis (L-IPF) questionnaire

**Measure:** Change in Living with Pulmonary Fibrosis (L-IPF) questionnaire score

**Time Frame:** 52 weeks

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients with a tertiary ILD centre diagnosis of fibrotic interstitial lung disease

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** alexandra.lawrence@gstt.nhs.uk

**Name:** Alexandra Lawrence, MBBS

**Phone:** 02071887188

**Phone Ext:** 58207

**Role:** CONTACT

**Contact 2:**

**Email:** gillian.radcliffe@gstt.nhs.uk

**Name:** Gillian Radcliffe, BSc

**Phone:** 07395285492

**Phone Ext:** 88070

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** London

**Country:** United Kingdom

**Facility:** Guy's & St Thomas' NHS Foundation Trust

**Zip:** SE1 9RT

#### Overall Officials

**Official 1:**

**Affiliation:** Guys and St. Thomas NHS Foundation Hospital

**Name:** Alex West, MBBS

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**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.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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.

**PMID:** 37187434

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006973

- Term: Hypertension

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000005355

- Term: Fibrosis

- ID: D000010335

- Term: Pathologic Processes

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000012818

- Term: Signs and Symptoms, Respiratory

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: HIGH

- As Found: Lung Disease

- ID: M8485

- Name: Fibrosis

- Relevance: LOW

- As Found: Unknown

- ID: M10027

- Name: Hypertension, Pulmonary

- Relevance: HIGH

- As Found: Pulmonary Hypertension

- ID: M19813

- Name: Lung Diseases, Interstitial

- Relevance: HIGH

- As Found: Interstitial Lung Disease

- ID: M14512

- Name: Pulmonary Fibrosis

- Relevance: HIGH

- As Found: Fibrosis Lung

- ID: M4185

- Name: Hypoxia

- Relevance: HIGH

- As Found: Hypoxemia

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15623

- Name: Signs and Symptoms, Respiratory

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008171

- Term: Lung Diseases

- ID: D000006976

- Term: Hypertension, Pulmonary

- ID: D000017563

- Term: Lung Diseases, Interstitial

- ID: D000011658

- Term: Pulmonary Fibrosis

- ID: D000000860

- Term: Hypoxia

### Misc Info Module

- Version Holder: 2024-05-31
