Clinical trial NCT03737409: PFOX: Pulmonary Fibrosis Ambulatory Oxygen Trial
Official title: PFOX: Pulmonary Fibrosis Ambulatory Oxygen Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fibrotic Interstitial Lung Disease
Lead sponsor: Monash University
Sponsor class: OTHER
First posted: 2018-11-09
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in physical activity measured by steps per day
timeFrame: Baseline, 3 month and 6 month assessments
Secondary outcomes:
measure: Change in functional exercise capacity assessed by 6-minute walk distance
timeFrame: Baseline, 3 month and 6 month assessments
measure: Change in health related quality of life evaluated using the St George's Respiratory Questionnaire
timeFrame: Baseline, 3 month and 6 month assessments
measure: Change in dyspnea measured using the Dyspnea-12 questionnaire
timeFrame: Baseline, 3 month and 6 month assessments
measure: Changes in fatigue evaluated by the Fatigue Severity Scale
timeFrame: Baseline, 3 month and 6 month assessments
measure: Change in anxiety and depression measured by the Hospital Anxiety and Depression Scale
timeFrame: Baseline, 3 month and 6 month assessments
measure: Change in time spent in moderate to vigorous physical activity
timeFrame: Baseline assessment, 3 month and 6 month assessments
measure: Change in sedentary time
timeFrame: Baseline assessment, 3 month and 6 month assessments
measure: Skeletal muscle metabolism
timeFrame: Baseline, 3 month and 6 month assessments
measure: Systemic inflammation
timeFrame: Baseline, 3 month and 6 month assessments
measure: Oxidative stress
timeFrame: Baseline, 3 month and 6 month assessments
measure: Use of oxygen therapy
timeFrame: 3 month and 6 month assessments
measure: Oxygen saturation in daily life
timeFrame: 3 month and 6 month assessments
measure: Incremental cost-effectiveness ratio
timeFrame: 6 month assessment
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Monash University
state: Victoria
Study officials:
affiliation: Monash University
name: Anne Holland, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.