INFINITE: A Phase III Randomised Crossover Trial of Domiciliary Nasal High Flow for Chronic Breathlessness in People with Interstitial Lung Disease.

Nasal High Flow (NHF) therapy is a non-invasive respiratory support device that delivers heated (32-37C) humidified, high flow (20-60 L/min) air through specialised nasal cannulae, with airflow generated from a flow generator system (myAirvoTM 3 system). All participants will have a baseline assessment performed at a single time point (measured once between Day -13 to Day 0). Baseline assessment will include a remote sleep study with a WatchPAT monitoring device, Respirasense respiratory monitoring device, and the Global Sleep Assessment Questionnaire (GSAQ), to be conducted in the patient’s home. Participants will then be randomly allocated according to the randomisation procedure to either: o Arm 1 – NHF therapy for 4 weeks, followed by usual care for 4 weeks with a one-week washout between periods. o Arm 2 – Usual care for 4 weeks, followed by NHF therapy for 4 weeks with a one-week washout between periods. At the start of the NHF Therapy intervention period, a respiratory nurse will commence the initial use of the intervention of NHF either in a study site (clinic) or home setting. There are no current published guidelines on NHF titration, and this will be individualised to each participant by a skilled senior respiratory clinical nurse. No oxygen will be entrained as eligible participants will not have severe resting hypoxemia based on SpO2 assessment at rest (SpO2 equal to or greater than 92%). Patients will be contacted at regular intervals (on day 3 of each treatment period and then every week for the remainder of the treatment period) during both the NHF therapy period and usual care period to troubleshoot device usage, prompt completion of daily VAS scores, and monitor adverse events. Participants will be able to telephone the respiratory nurse at other times for any device issues on a non-urgent basis (within 1 business day; as per current usual practice with home respiratory supports). From a safety perspective discontinuing either NHF without oxygen entrained does not have significant clinical consequences. NHF use will be recommended for 7 hours over 24 hours (ideally overnight). Current medications can continue. Rescue medications if used will be monitored. Patient reported outcomes will be assessed at the end of each 4-week period. Participants will be invited to participate in a semi-structured interview about their experiences with NHF at the conclusion of their NHF therapy period (either during the washout week or during the follow-up week dependent on randomisation).