Distinct physiological effects of high-flow nasal cannula, helmet CPAP, and their combination in acute hypoxemic respiratory failure

ISRCTN	ISRCTN15358358
DOI	https://doi.org/10.1186/ISRCTN15358358
OSF preregistration	https://doi.org/10.17605/OSF.IO/G9BYC
Sponsor	Ospedale Santa Chiara
Funder	Ministero della Salute

Submission date: 07/05/2026
Registration date: 08/06/2026
Last edited: 20/07/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Sergio Lassola
Public, Scientific, Principal investigator

Department of Anesthesia and Intensive Care 1
Santa Chiara Hospital, APSS
Largo Medaglie d’Oro 9
Trento
38122
Italy

ORCID ID	0000-0002-6088-670X
Phone	+390461 902579
Email	sergio.lassola@asuit.tn.it

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Crossover
Purpose	Treatment
Participant information sheet	49480_PIS_v1.0_01Feb2023.pdf
Scientific title	Physiological comparison of high-flow nasal cannula, helmet CPAP and their combination in acute hypoxemic respiratory failure: a crossover physiological study
Study acronym	HFNC-HELMET Study
Study objectives	To compare the physiological effects of high-flow nasal cannula (HFNC), helmet CPAP (H-CPAP), and their combination (HFNC+CPAP) on inspiratory effort, respiratory mechanics, and gas exchange in ICU patients with acute hypoxemic respiratory failure
Ethics approval(s)	Approved 26/02/2024, Ethics Committee for Clinical Trials – Province of Trento (Comitato Etico per la Sperimentazione Clinica – Provincia di Trento) (Via Gilli 4, Trento, 38121, Italy; +39 0461 904111; comitato.etico@apss.tn.it), ref: #4638-26/02/2024
Health condition(s) or problem(s) studied	Acute hypoxemic respiratory failure in ICU patients
Intervention	The study was designed as a randomized crossover physiological investigation. The sequence of the three interventions (HFNC, Helmet CPAP, HFNC+CPAP) was randomized using a computer-generated randomization sequence created with Random.org. Allocation was generated before study procedures and applied sequentially for each enrolled patient. Enrolled ICU patients undergo three interventions in random order: High-flow nasal cannula (HFNC) at 50 L/min; Helmet CPAP (H-CPAP) with PEEP 8 cmH2O and total flow 80 L/min; Combined HFNC+CPAP with HFNC delivered inside the helmet. Each intervention lasts 30 minutes. Inspiratory effort, respiratory mechanics, ventilatory pattern, and gas exchange are measured during each phase.
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	High-flow nasal cannula (HFNC), Helmet CPAP (H-CPAP), combined HFNC+CPAP support
Primary outcome measure(s)	Inspiratory effort measured using Esophageal pressure swing (ΔPes) and simplified esophageal pressure–time product per minute (sPTPes/min) measured using esophageal manometry, at each 30-minute intervention phase (HFNC, H-CPAP, HFNC+CPAP)
Key secondary outcome measure(s)	Gas exchange and respiratory mechanics measured using PaO₂/FiO₂ ratio, venous admixture, PaCO₂, respiratory rate, tidal volume, minute ventilation, dynamic transpulmonary driving pressure (ΔPL), and dynamic lung compliance, at the final 5 minutes of each 30-minute intervention phase. Ventilatory load measured using the respiratory rate, minute ventilation (Ve), and Ve corrected for PaCO₂ at each 30-minute intervention phase Oxygenation measured using PaO₂/FiO₂ ratio and venous admixture obtained from arterial blood gas analysis, at the final 5 minutes of each intervention phase Pneumatic performance of PEEP valves measured using airway pressure swing (ΔPaw) and correlation between ΔPaw and ΔPes using flow-dependent and flow-independent PEEP valves, at H-CPAP and HFNC+CPAP phases Non-invasive ventilation (NIV) failure measured using data on the need for endotracheal intubation after non-invasive respiratory support, at within 48 hours after study completion Patient comfort and dyspnea measured using the Borg dyspnea and discomfort scales, at each intervention phase
Completion date	01/01/2025

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	99 Years
Sex	All
Target sample size at registration	18
Total final enrolment	18
Key inclusion criteria	1. Adult ICU patients with acute hypoxemic respiratory failure requiring supplemental oxygen therapy to maintain PaO₂ >60 mmHg or SpO₂ >90%, PaCO₂ <45 mmHg 2. Respiratory rate >25 breaths/min 3. Acute onset of symptoms within 7 days of hospital admission 4. Age >18 years
Key exclusion criteria	1. Asthma or COPD exacerbation 2. Cardiogenic pulmonary edema 3. Chronic neuromuscular disease 4. Pulmonary embolism 5. Pregnancy
Date of first enrolment	08/03/2024
Date of final enrolment	01/01/2025

Locations

Countries of recruitment

Italy

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other files			13/05/2026	No	No
Participant information sheet	Italian version 1.0	01/02/2023	13/05/2026	No	Yes
Protocol file	Italian	26/04/2023	07/05/2026	No	No
Protocol file	English	26/04/2023	20/07/2026	No	No
Statistical Analysis Plan			13/05/2026	No	No

Additional files

49480_Protocol_26April2023.pdf: Italian
49480_SAP.pdf: Statistical Analysis Plan
49480_CaseReportForm Helmet SS [Italian].pdf: Other files
49480_PIS_v1.0_01Feb2023.pdf: Italian
49480_Protocol_26Apr2023_EN.pdf: English

Editorial Notes

20/07/2026: Protocol uploaded.
07/05/2026: Study’s existence confirmed by the Ethics Committee for Clinical Trials – Province of Trento (Comitato Etico per la Sperimentazione Clinica – Provincia di Trento), Italy.