FIBRotic Interstitial Lung Disease With Nocturnal hypOXaemia and EXercise Induced desaTuRAtion

Pulmonary Hypertension Clinical Trial

— FIBRINOX-EXTRA  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06416163
• Other study ID #: 329843
• Status: Not yet recruiting
• Start date: July 1, 2024
• Est. completion date: July 1, 2029

Study information

• Verified date: May 2024
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: Alexandra Lawrence, MBBS
• Phone: 02071887188
• Email: alexandra.lawrence[@]gstt.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: July 1, 2029
• Est. primary completion date: October 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis Lung
• Hypertension, Pulmonary
• Hypoxia
• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis
• Pulmonary Hypertension

Intervention

Other:
• Prospective
Collection of prospective data all ready available for participant

Locations

Country	Name	City	State
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	Boehringer Ingelheim

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 6-minute walk distance	As measured by 6-minute walk test	52 weeks
Secondary	Mortality	If death occurs during the study period, and the cause of death	52 and 156 weeks
Secondary	Clinical deterioration	Defined by: decline in forced vital capacity (FVC) >10% or death	52 weeks
Secondary	Decline in FVC	Decline in forced vital capacity	52 weeks
Secondary	Decline in TLCO	Decline in total diffusing capacity of the lungs for carbon monoxide	52 weeks
Secondary	Pulmonary hypertension	Right heart catheter confirmed pulmonary hypertension	52 and 156 weeks
Secondary	Change in arterialised capillary blood gas pO2	Arterialised capillary blood gas partial pressure of oxygen	52 weeks
Secondary	Change in arterialised capillary blood gas oxygen saturations	Arterialised capillary blood gas oxygen saturations	52 weeks
Secondary	Change in arterialised capillary blood gas pCO2	Arterialised capillary blood gas partial pressure of carbon dioxide	52 weeks
Secondary	Change in arterialised capillary blood gas HCO3	Arterialised capillary blood gas partial pressure of bicarbonate	52 weeks
Secondary	Change in arterialised capillary blood gas pH	Arterialised capillary blood gas pH	52 weeks
Secondary	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
Secondary	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
Secondary	Change in NT-proBNP/BNP level	Change in NT-proBNP/BNP level from baseline	52 weeks
Secondary	Change in troponin level	Change in troponin level from baseline	52 weeks
Secondary	Change in peak TRV	Change in peak tricuspid regurgitation velocity (TRV)	52 weeks
Secondary	Change in cardiac chamber size/area	Change in cardiac chamber size/area	52 weeks
Secondary	Change in cardiac chamber area	Change in cardiac chamber area	52 weeks
Secondary	Change in RV/LV basal diameter area ratio	Change in right ventricle to left ventricle basal diameter area ratio	52 weeks
Secondary	Change in MPA:AA diameter ratio	Change in main pulmonary artery to ascending aorta diameter ratio	52 weeks
Secondary	Change in TAPSE/sPAP ratio	Change in tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio	52 weeks
Secondary	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
Secondary	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
Secondary	Change in Living with Pulmonary Fibrosis (L-IPF) questionnaire score	Change in score of Living with Pulmonary Fibrosis (L-IPF) questionnaire	52 weeks