BACKGROUND: Despite a lack of evidence, ambulatory oxygen therapy is frequently prescribed for patients with interstitial lung disease (ILD) and exertional desaturation. Patients often prefer portable oxygen concentrators to oxygen cylinders. This study aimed to examine the feasibility of conducting a clinical trial of ambulatory oxygen delivered via portable concentrators in patients with ILD.METHODS: In this randomised, triple-blinded, sham-controlled trial, 30 participants with ILD and isolated exertional desaturation to <90% on 6-minute walk tests were randomised to 12-week ambulatory oxygen or air delivered via portable concentrators, with assessments performed at baseline and Weeks 4, 12 and 18. Primary outcomes were trial feasibility and the change in 6-minute walk distance (6MWD) on room air at Week 12.FINDINGS: Study recruitment was completed within 18 months, with six withdrawals. Participant blinding was successful, with the Bang's Blinding Index being 0 (95% CI -0.40, 0.40) for the oxygen group and 0 (-0.42, 0.42) for the sham group. There was no significant difference in 6MWD between groups at Week 12 (mean difference of -34m [95% CI: -105, 36], p = 0.34). For secondary outcomes, compared to the sham group, the oxygen group had a significantly higher Leicester Cough Questionnaire psychological domain score, indicating better cough-related quality of life (mean difference of 0.9 [95% CI: 0.2, 1.6], p = 0.01), but a shorter duration of moderate-to-vigorous activities (mean difference of -135 [95% CI: -267, -3], p = 0.04) at Week 12.CONCLUSION: Based on the results of this pilot study, a definitive randomised controlled trial with a longer intervention duration is warranted to clarify therapeutic impacts of ambulatory oxygen in patients with ILD.