Benefit of High-flow Nasal Cannula on Persistent Dyspnea in Ild (HIGHOXFILD)

Benefit of High-flow Nasal Cannula on Persistent Dyspnea in Interstitial Lung Disease: Randomized Multicentric Cross-over Trial

The main purpose of this study is to evaluate the effects of high-flow nasal therapy (HFNT) oxygen compared to long-term oxygen therapy (LTOT) on dyspnea and quality of life in intersititial lung disease patients with chronic respiratory failure and persistent breathlessness in whom LTOT has already been initiated.

Study Overview

• Status: Not yet recruiting
• Conditions: ILD
• Intervention / Treatment: Procedure: long-term oxygen therapy (LTOT); Procedure: High Flow Nasal Therapy (HFNT)

Detailed Description

The study will be a non-blinded, two-arm, crossover (2 periods of 2 weeks each), randomised controlled superiority multicentre trial comparing the effect of HFNT on persistent dyspnoea in intersititial lung disease patients with chronic respiratory failure as compared to LTOT over a two-week period. The oxygen flow rate with HFNT will be the same as for usual care. The HFNT will be used during the night and during the 3-minute chair rise test, it can be used during the day depending on the patient's needs. During the rest of the time, the LTOT will be used as in usual care. Participants will be randomised to receive (1) 2 weeks of LTOT then 2 weeks of LTOT+HFNT or (2) 2 weeks of LTOT+HFNT then 2 weeks of LTOT. The investigators will determine the effect of HFNT on quality of life and dyspnoea. The investigators will also study the effect of HFNT on secondary outcomes listed below. Each assessment will be performed at the end of each 2-week period. Polysomnography will be optional. The study will be conducted in 42 patients with LTOT suffering from persistent breathlessness.

With a total sample of 38 patients and a crossover design, if the real difference on the Saint George's Respiratory Questionnaire (SGRQ) is 6, the standard deviation of the matched difference is 12.5 and the significance threshold is 5%, a two-tailed Student's t test will have a power of 80% to conclude that the difference is significantly different from 0 (Calculated using PASS 14.0.14, Analysis of a cross-over design using difference).These hypotheses are based on the values observed in the article by Nagata et al. (PMID: 29283682), in patients with Chronic Obstructive Pulmonary Diseaes of the same severity, which reported an improvement in the SGRQ-s of -10.8 (95% CI: -15.3; -6.3, i.e. SD of 12.4) with HFNT administered at night for 6 weeks versus LTOT Another study (PMID: 31308647) reported an improvement of -11.9 (CI95% -17.2; -6.6) after an introduction of HFNT. As the minicmal clinical improvement difference for SGRQ is 4, a difference of 6 is considered was both realistic and clinically relevant. A Student's t test allows a conservative approach compared to the use of a linear mixed-effects model retained for the analysis of the primary endpoint.

To take account of reduced precision due to possible loss of follow-up or study withdrawals, the sample was increased by 10%, i.e. 42 patients: 21 in the HFNT+LTOT then LTOT sequence and 21 in the LTOT then HFNT+LTOT sequence.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Capucine Morélot-Panzini, MD,PhD, Prof; Phone Number: 0142167771; Email: capucine.morelot@aphp.fr
• Study Contact Backup: Name: Anne Radenne; Phone Number: 0142161699; Email: anne.radenne@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Intertitial lung disease
• Persistant dyspnea (mMRC≥3)
• Long-term oxygen therapy at least for 3 months

Exclusion Criteria:

• Chronic respiratory disease (COPD, lung cancer)
• Pneumothorax,
• Pneumomediastinum,
• Active smoker,
• Patient on non-invasive ventilation or continuous positive airway pressure (CPAP),
• Pregnancy or breastfeeding,
• Unable to read or understand questionnaires,
• No written consent,
• Patients under guardianship,
• No health assurance coverage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Long-Term Oxygen therapy (LTOT) then High Flow Nasal Therapy (HFNT); 2 weeks of LTOT then 2 weeks of LTOT+HFNT	Procedure: long-term oxygen therapy (LTOT); Usual care with LTOT for 2 weeks; Procedure: High Flow Nasal Therapy (HFNT); High Flow Nasal delivered by myAirvo3 (4 hours minimum and during th 3-minute chair rise test, 30L/min, 34°C, identical O2 flow rate as LTOT) for 2 weeks
Other: High Flow Nasal Therapy (HFNT) then Long-Term Oxygen therapy (LTOT); 2 weeks of LTOT+HFNT then 2 weeks of LTOT	Procedure: long-term oxygen therapy (LTOT); Usual care with LTOT for 2 weeks; Procedure: High Flow Nasal Therapy (HFNT); High Flow Nasal delivered by myAirvo3 (4 hours minimum and during th 3-minute chair rise test, 30L/min, 34°C, identical O2 flow rate as LTOT) for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SGRQ questionnaire : Saint George's Respiratory Questionnaire (symptom component)	Symptom component of SGRQ : Scores range from 0 to 100, with higher scores indicating more limitations.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyspnea assessement : dyspnoea-12	Dyspnea-12 score range from 0 to 36, with higher score indicating worse breathlessness	2 weeks
Dyspnea assessement : mMRC: Modified Medical Research Council	mMRC score : range frome 0 (low) to 4(high) and assesses the intensity of dyspnea	2 weeks
Dyspnea assessement : MDP: Multidimensional dyspnea profile	Immediate affective score range from 0 to 10 with higher score indicating worse breathlessness; Sensory score range from 0 to 50 with higher score indicating worse breathlessness; Emotional score range from 0 to 50 with higher score indicating worse breathlessness	2 weeks
Quality of life (SGRQ questionnaire) : S.George's Respiratory Questionnaire	Total score range from 0 to 100 with higher score indicating more limitations; Activity subscore range from 0 to 100 with higher score indicating more limitations; Impact sub-score range from 0 to 100 with higher score indicating more limitations	2 weeks
Quality of life (K-Bild) : The King's Brief Interstitial Lung Disease (KBILD) questionnaire	Total score range from 0 to 100 with lower score indicating more limitations	2 weeks
Quality of life questionnaire (SF12): Short Form 12	Total score range from 0 to 100 with higher score indicating more limitations	2 weeks
Anxiety-depression (HADS) : Hospital Anxiety and Depression scale	Anxiety sub-score range from 0 to 21 with higher score indicating more severe anxiety; Depression sub-scorerange from 0 to 21 with higher score indicating more severe depression	2 weeks
Distance at 6-minutes walk test	Length in meters	2 weeks
Dyspnea (Borg score) at the 6-minutes walk test	Score range from 0 to 10 with higher score indicating worst breathlessness	2 weeks
Number of rise at the 3-minutes rise chair test	Number of rise	2 weeks
Dyspnea (Borg score) at the 3-minutes rise chair test	Score range from 0 to 10 with higher score indicating worst breathlessness	2 weeks
Nocturnal capnography	Mean PtcCO2	2 weeks
Respiratory rate	Mean day-time respiratory rate measured by a wearable tele-monitoring device (breaths/min); Mean night-time respiratory rate measured by a wearable tele-monitoring device (breaths/min)	Over 2 weeks
Heart rate	Mean day-time heart rate measured by a wearable tele-monitoring device (beats/min); Mean night-time heart rate measured by a wearable tele-monitoring device (beats/min)	Over 2 weeks
SpO2	Mean day-time SpO2 measured by a wearable tele-monitoring device (%); Mean night-time SpO2 measured by a wearable tele-monitoring device (%)	Over 2 weeks
Rest	Mean daily rest hours measured by a wearable tele-monitoring device (hours/day)	Over 2 weeks
Activity	Mean daily walking hours measured by a wearable tele-monitoring device (hours/day)	Over 2 weeks
Activity	Mean daily steps measured by a wearable tele-monitoring device (steps/day)	Over 2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Sleep duration (minutes)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Onset latency (minutes)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Percentage of REM sleep (%)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Sleep efficiency (%)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Apnoea-hypopnoea index (per hour)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Index of arousal and micro-arousals (per hour)	2 weeks
Sleep Quality only in patients for whom nocturnal polysomnography is performed during one night (optional)	Time spent at SpO2 below 90% (TST90) (%)	2 weeks
Acute exacerbation and/or increase in resting oxygen flow	Number of patients with (i) an acute exacerbation defined as the onset or acute worsening of dyspnoea, associated with an increase in radiological lesions (new ground-glass opacities and/or bilateral condensations) not explained by heart failure or overload, or (ii) an increase in resting oxygen flow of more than 2 L/min (on medical prescription).	2 weeks
HFNT(High Flow Nasal Therapy) compliance	Average daily hours of use of the HFNT device; Average daily hours of use of LTOT	2 weeks
HFNT (High Flow Nasal Therapy) acceptability	Side effects	2 weeks

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Capucine Morélot-Panzini, MD,PhD, Prof, APHP • Assistance Publique des hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2024
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ILD; Chronic breathlessness; high nasal flow canula
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Dyspnea
• Other Study ID Numbers: APHP210079; IDRCB (Other Identifier: 2025-A02589-40)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatiqueet des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No