PFOX: Pulmonary Fibrosis Ambulatory Oxygen Trial

NCT ID: NCT03737409

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2024-07-31

Brief Summary

The fibrotic interstitial lung diseases (fILD) are characterised by lung scarring, distressing breathlessness and poor health-related quality of life. Exertional desaturation (low blood oxygen during exercise) is a hallmark of fILD, occurring in over 50% of patients. It is sometimes treated with ambulatory oxygen therapy (AOT), which involves breathing supplemental oxygen during physical activity. However the absence of clinical trials has given rise to marked variations in policy and practice globally. Even where AOT is available, treatment adherence using the traditional delivery method of cylinder gas is poor. Recently new devices called portable oxygen concentrators (POCs), have become available, which are lighter and more maneuverable than a cylinder. This may enhance adherence and maximize treatment benefits.

This trial will determine the clinical benefits and societal costs of AOT for people with fILD and exertional desaturation. A randomised controlled trial with blinding of participants, assessors and clinicians, and an embedded economic evaluation will be conducted. A total of 260 participants with fILD and exertional desaturation will be randomly assigned to use either AOT or air delivered using a POC for 6 months. If this trial demonstrates clinical and economic benefits of AOT then the findings can be rapidly translated into practice.

Detailed Description

Interstitial lung diseases (ILDs) are characterized by scarring of lung tissue. Stiffening of the lungs leads to reduced transfer of oxygen into the blood, decreased exercise capacity and premature death. Around 85% of the ILDs are known as fibrotic ILD (fILD), a form of ILD which tends to have worse outcomes than other types of ILD. People with fibrotic ILD often experience distressing breathlessness, cough and fatigue; loss of independence and life roles; financial strain; and unpleasant treatment side effects.The most common of the fILDs is idiopathic pulmonary fibrosis (IPF), which has an average survival of 3 years from diagnosis. Recently, two new treatments have been shown to halve the annual decline in lung function in mild to moderate IPF, making it a 'treatable' condition for the first time. However, these treatments only slow the decline in lung function; they do not stabilize or reverse it, nor do patients experience improved quality of life or breathlessness.

For people with fILD who have abnormally low oxygen in the blood at rest, long term oxygen therapy (LTOT, used ≥18 hours per day) is strongly recommended, based on survival benefits in studies of people with chronic obstructive pulmonary disease (COPD). However, for people with fILD who have low oxygen levels only during exertion, the role of oxygen therapy is not clear.

Ambulatory oxygen therapy (AOT), defined as the use of oxygen during exercise and activities of daily living, has historically been used to improve blood oxygen levels and exercise capacity. However, many people with fILD find this treatment difficult to use. Oxygen cylinders are heavy and run out quickly, therefore patient burden often exceeds any benefits. Portable oxygen concentrators (POCs) are newly available, lighter and rechargeable. However there are potential disadvantages to POCs. Generally, they deliver oxygen in pulses, which is where oxygen is delivered only when breathing in, and they do not deliver 100% oxygen. Doctors often express concerns that POCs cannot meet the demands of people with fILD during exercise. Recently it was shown that people with fILD who use a POC have similar blood oxygen levels to those who use a cylinder during exercise, suggesting that this might be a useful treatment.

This study will examine the benefits and costs of ambulatory oxygen, delivered using a POC, in people with fILD and exertional desaturation. The aim is to compare the impact of AOT vs air in people with fILD who have low blood oxygen during exercise, and to compare the cost-effectiveness of AOT and air in fILD. A total of 260 people with fILD will be invited to participate. The trial will be conducted at four sites in Australia and two sites in Sweden. Participants will be randomly allocated into two groups; Group 1 will be administered AOT using a POC (AOT group); and Group 2 will be administered sham AOT using an identical POC (air group). Participants, health professionals and trial staff will not be aware of which POC is being used. The allocated treatment will be delivered for 6 months. Measurements of physical activity during daily life, symptoms, exercise capacity and HRQOL will be collected at the beginning of the trial, and 3 and 6 months after treatment has commenced. Information about use of health care services, both from hospital records and directly from participants will also be collected.

Conditions

Fibrotic Interstitial Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oxygen therapy with POC (AOT group)

Patients will receive ambulatory oxygen therapy provided by a portable oxygen concentrator and will be encouraged to use it at all times when they are moving about, including walking at home or in the community, during exercise or during other activities.

Group Type: EXPERIMENTAL

Ambulatory Oxygen Therapy

Intervention Type: OTHER

Supplemental oxygen delivered during exercise and activities of daily living via a portable oxygen concentrator

Sham oxygen therapy with POC (air group)

Patients will receive sham ambulatory oxygen therapy provided by a portable oxygen concentrator and will be encouraged to use it at all times when they are moving about, including walking at home or in the community, during exercise or during other activities.

Group Type: SHAM_COMPARATOR

Sham Ambulatory Oxygen Therapy

Intervention Type: OTHER

Air delivered during exercise and activities of daily living via a portable oxygen concentrator that has been modified to deliver air

Interventions

Ambulatory Oxygen Therapy

Supplemental oxygen delivered during exercise and activities of daily living via a portable oxygen concentrator

Intervention Type: OTHER

Sham Ambulatory Oxygen Therapy

Air delivered during exercise and activities of daily living via a portable oxygen concentrator that has been modified to deliver air

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of Fibrotic Interstitial Lung Disease
• Stable pharmacotherapy over the last 3 months
• Exertional desaturation (SpO2≤88% for at least 10 consecutive seconds) during a 6 Minute Walking Test performed on room air

Exclusion Criteria

• Currently using or eligible for long term oxygen therapy (PaO2≤55 mmHg at rest on room air, or 56-59 mmHg with evidence of right heart failure)
• Current smokers
• Pregnant patients
• Patients cognitively unable to consent; or if death or transplant is anticipated within the study period.
• Participants currently in pulmonary rehabilitation
• Non-ambulant patients
• Admission to an acute care hospital within the last 30 days

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Monash University

OTHER

Sponsor Role: lead

Responsible Party

Anne E Holland PhD, FThorSoc

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne Holland, Professor

Role: PRINCIPAL_INVESTIGATOR

Monash University

Locations

Monash University

Melbourne, Victoria, Australia

Countries

Australia

References

Kawachi S, Hoffman M, Holland AE. Clinical Features Associated With Fatigue in People With Fibrotic Interstitial Lung Disease: Cross-Sectional Study. Respirology. 2025 Jul 20. doi: 10.1111/resp.70091. Online ahead of print.

Reference Type: DERIVED

PMID: 40685600 (View on PubMed)

Hoffman M, Burge AT, Wong N, McDonald CF, Chambers DC, Glaspole I, Mackintosh JA, Ekstrom M, Skold M, Goh NSL, Corte TJ, Holland AE. Exertional Desaturation During the 6-Minute Walk Test vs Daily Life in People With Fibrotic Interstitial Lung Disease. Chest. 2024 Mar;165(3):632-635. doi: 10.1016/j.chest.2023.08.024. Epub 2023 Sep 1. No abstract available.

Reference Type: DERIVED

PMID: 37659620 (View on PubMed)

Holland AE, Corte T, Chambers DC, Palmer AJ, Ekstrom MP, Glaspole I, Goh NSL, Hepworth G, Khor YH, Hoffman M, Vlahos R, Skold M, Dowman L, Troy LK, Prasad JD, Walsh J, McDonald CF. Ambulatory oxygen for treatment of exertional hypoxaemia in pulmonary fibrosis (PFOX trial): a randomised controlled trial. BMJ Open. 2020 Dec 13;10(12):e040798. doi: 10.1136/bmjopen-2020-040798.

Reference Type: DERIVED

PMID: 33318119 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HREC/18/Alfred/42

Identifier Type: -

Identifier Source: org_study_id