Respiratory FailureHENIVOT2NCT05089695
Helmet NIV vs. CPAP vs. High-flow Nasal Oxygen in Hypoxemic Respiratory Failure
A study testing Noninvasive respiratory support in people with Respiratory Failure and Hypoxemic Respiratory Failure, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Multicenter, open label, three-arm randomized trial to assess the effect of helmet noninvasive ventilation vs. helmet continuous positive airway pressure vs. high-flow nasal oxygen on the rate of endotracheal intubation of patients with acute moderate-to-severe hypoxemic respiratory failure Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure, Hypoxemic Respiratory Failure
- What is being tested?
- Noninvasive respiratory support
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,200 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2022to Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute symptoms of respiratory failure PaO2/FiO2 ratio ≤ 200; PaCO2≤45mmHg; Absence of history of chronic respiratory failure or moderate to severe cardiac insufficiency (NYHA>2 or left ventricular ejection fraction<50%); Informed consent
- Patients that have already received NIV, CPAP continuously for more than 24 hours before the screening visit will be excluded.
- Other Exclusion Criteria:
- Pregnancy;
- Exacerbation of asthma or chronic obstructive pulmonary disease;
- Hypercapnia (PaCO2>45 mmHg) with or without respiratory acidosis;
Show all 20Show fewer
- More than 2 organ failures, including the lung.
- Documented pneumothorax;
- Clinical diagnosis of Cardiogenic pulmonary edema;
- Haemodynamic instability (Systolic blood pressure<90 mmHg or mean arterial pressure<65mmHg) and/or lactic acidosis (lactate>5 mmol/L) and/or clinically diagnosed Shock requiring administration of vasoactive agents (norepinephrine>0.1 mcg/Kg/min);
- Metabolic Acidosis (pH <7.30 with normal- or hypo-carbia);
- Chronic kidney failure requiring dialysis before ICU admission;
- Chronic hypoxemic respiratory failure requiring long-term oxygen therapy;
- Altered neurological status that requires immediate intubation and/or making the patient uncooperative;
- Urgent need for endotracheal intubation, according to the decision of the attending physician;
- Do not intubate order;
- Decision of withdrawal of life-sustaining therapy;
- Thoracic or abdominal surgery in the previous 7 days;
- Any condition that makes the patient very likely to require endotracheal intubation due to a reason different from respiratory failure;
- Recent head surgery or anatomy that prevent the application of helmet or HFNC to patient's face.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Gemelli
Rome
Domenico L Grieco, MD, dlgrieco@outlook.it
About this study
Official title: Helmet Noninvasive Ventilation vs. Continuous Positive Airway Pressure vs. High-flow Nasal Oxygen as First-line Treatment of Acute Hypoxemic Respiratory Failure (HENIVOT2). An Open-label, Multicentre Randomized Trial
Multicenter, open label, three-arm randomized trial to assess the effect of helmet noninvasive ventilation vs. helmet continuous positive airway pressure vs. high-flow nasal oxygen on the rate of endotracheal intubation of patients with acute moderate-to-severe hypoxemic respiratory failure
Read the detailed description
The optimal initial management of acute hypoxemic respiratory failure is uncertain. Helmet noninvasive ventilation and high-flow nasal oxygen appear as the most promising techniques in this setting. Recently, the first head-to-head randomized trial compared first-line continuous treatment with helmet pressure support ventilation with specific settings (PEEP=12 cmH2O pressure and pressure support=10-12 cmH2O) vs. high-flow nasal oxygen alone in patients with moderate-to-severe hypoxemic respiratory failure. Results showed no significant inter-group difference in the days free of respiratory support at 28 days, but lower intubation rate and increased 28-day invasive ventilation-free days in the helmet group. Use of helmet noninvasive ventilation is less frequent than use of helmet continuous positive airway pressure, which is simpler to use.
The investigators designed an open-label, multicentre randomized trial to assess the effect of helmet pressure support ventilation and continuous airway pressure as compared to high-flow nasal oxygen on the intubation rate of patients with moderate-to-severe hypoxemic respiratory failure in the intensive care unit.
- Conditions
- Respiratory Failure, Hypoxemic Respiratory Failure
- Being tested
- Noninvasive respiratory support
- Keywords
- Noninvasive ventilation, High-flow nasal oxygen, Mechanical ventilation
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Noninvasive respiratory supportDevice
Treatment of acute hypoxemic respiratory failure
| Study group | Role | What they receive |
|---|---|---|
| Helmet Noninvasive ventilation (NIV) | Experimental | Patients in helmet noninvasive ventilation group will receive continuous helmet pressure support ventilation for at least 16 hours/day in the first 2 calendar days. Dedicated helmets for noninvasive ventilation will be applied and size will be chosen according to patient's neck circumference.
Each patient will be connected to a mechanical ventilator ventilator through a bitube circuit with no humidification.
The ventilator will be set in PSV-NIV mode, with the following suggested settings [34-38]:
1. initial pressure support=12 cmH2O and adequate to permit a peak inspiratory flow of 100 l/min;
2. positive end-expiratory pressure=12 cmH2O.
3. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%.
4. Inspiratory flow trigger = 2 l/min or according to the practice of each institution;
5. fastest pressurization time;
6. expiratory trigger: 10-50% of the maximum inspiratory flow, eventually modified to avoid double triggering;
7. maximum inspiratory time 1.2 second. Receives: Device: Noninvasive respiratory support |
| Helmet continuous airway pressure (CPAP) | Experimental | Patients in CPAP group will receive continuous helmet CPAP for at least 16 hours/day in the first 2 calendar days. Continuous CPAP without interruptions will be strongly encouraged in the first 48 hours of treatment. Dedicated helmets for noninvasive ventilation will be applied and size will be chosen according to patient's neck circumference.
Treatment will be delivered through a high-flow generator. The following settings will be applied:
1. Continuous air flow>45 l/min.
2. Bi-tube circuit with no humidification, Y-piece with heat and moisture exchanger, or active heating and humidification with humidification chamber temperature set at 31 °C, 34 °C or 37 °C according to patients' comfort.
3. Expiratory positive end-expiratory pressure valve set to achieve PEEP=12 cmH2O.
4. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%. Receives: Device: Noninvasive respiratory support |
| High-flow nasal oxygen | Active comparator | Initial set flow will be 50-60 l/min and flows will be decreased. in case of intolerance and/or according to patients' requirements: flows≥30 L/min will be mandatory in all enrolled patients. Humidification chamber will be set at 31 °C, 34 °C or 37 °C according to patient's comfort. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%.
Weaning the patient from high-flow will be considered only after 48 hours from enrolment and will be discouraged until the patients is considered for ICU discharge. Receives: Device: Noninvasive respiratory support |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Endotracheal intubation
The proportion of patients requiring endotracheal intubation according to predefined criteria
Measured: 28 days
Secondary outcomes (11)
Days free of invasive mechanical ventilation at day 28
The number of days in which patients do not receive mechanical ventilation within 28 days from randomization
Measured: 28 days
Days free of invasive mechanical ventilation at day 60
The number of days in which patients do not receive mechanical ventilation within 60 days from randomization
Measured: 60 days
Days free of invasive mechanical ventilation at day 90
The number of days in which patients do not receive mechanical ventilation within 60 days from randomization
Measured: 90 days
Rate of In-intensive care unit mortality
All-cause mortality, assessed at the discharge from the intensive care unit
Measured: 90 days
Rate of In-hospital care unit mortality
All-cause mortality, assessed at the discharge from the hospital
Measured: 90 days
Rate of 90-day mortality
All-cause 90-day mortality
Measured: 90 days
90-day ICU free days
The days not spent in the intensive care unit by the patient on a 90-day basis
Measured: 90 days
90-day hospital free days
The days not spent in the hospital by the patient on a 90-day basis
Measured: 90 days
Incidence of pneumonia
Incidence of pneumonia, diagnosed after the treatment start and during the ICU stay
Measured: 90 days
Incidence of shock
Incidence of shock, diagnosed after treatment start and during the ICU stay
Measured: 90 days
Incidence of barotrauma
Incidence of barotrauma, defined as pneumothorax o pneumomediastinum after treatment start and during the ICU stay
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start1 Mar 2022
- Primary completionDec 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva, Catholic University of the Sacred Heart
- Responsible party
- Sponsor
- Investigators
- Domenico Luca Grieco, MD, Principal investigator, Fondazione Policlinico A. Gemelli IRCCSMassimo Antonelli, MD, Study chair, Fondazione Policlinico A. Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05089695
- Sponsor's protocol ID
- HENIVOT2
- Acronym
- HENIVOT2
- Status last verified
- Sep 2025
- First submitted
- 11 Oct 2021
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual data will be made available by the principal investigator upon a reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Helmet Noninvasive Ventilation vs. Continuous Positive Airway Pressure vs. High-flow Nasal Oxygen as First-line Treatment of Acute Hypoxemic Respiratory Failure (HENIVOT2). An Open-label, Multicentre Randomized Trial
- ClinicalTrials.gov ID
- NCT05089695
- Acronym / sponsor ID
- HENIVOT2 / HENIVOT2
- Conditions
- Respiratory Failure, Hypoxemic Respiratory Failure
- Keywords
- Noninvasive ventilation, High-flow nasal oxygen, Mechanical ventilation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva, Catholic University of the Sacred Heart
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 22 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicenter, open label, three-arm randomized trial to assess the effect of helmet noninvasive ventilation vs. helmet continuous positive airway pressure vs. high-flow nasal oxygen on the rate of endotracheal intubation of patients with acute moderate-to-severe hypoxemic respiratory failure
Detailed description
The optimal initial management of acute hypoxemic respiratory failure is uncertain. Helmet noninvasive ventilation and high-flow nasal oxygen appear as the most promising techniques in this setting. Recently, the first head-to-head randomized trial compared first-line continuous treatment with helmet pressure support ventilation with specific settings (PEEP=12 cmH2O pressure and pressure support=10-12 cmH2O) vs. high-flow nasal oxygen alone in patients with moderate-to-severe hypoxemic respiratory failure. Results showed no significant inter-group difference in the days free of respiratory support at 28 days, but lower intubation rate and increased 28-day invasive ventilation-free days in the helmet group. Use of helmet noninvasive ventilation is less frequent than use of helmet continuous positive airway pressure, which is simpler to use.
The investigators designed an open-label, multicentre randomized trial to assess the effect of helmet pressure support ventilation and continuous airway pressure as compared to high-flow nasal oxygen on the intubation rate of patients with moderate-to-severe hypoxemic respiratory failure in the intensive care unit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Helmet Noninvasive ventilation (NIV) | Experimental | Device: Noninvasive respiratory supportPatients in helmet noninvasive ventilation group will receive continuous helmet pressure support ventilation for at least 16 hours/day in the first 2 calendar days. Dedicated helmets for noninvasive ventilation will be applied and size will be chosen according to patient's neck circumference. Each patient will be connected to a mechanical ventilator ventilator through a bitube circuit with no humidification. The ventilator will be set in PSV-NIV mode, with the following suggested settings [34-38]: 1. initial pressure support=12 cmH2O and adequate to permit a peak inspiratory flow of 100 l/min; 2. positive end-expiratory pressure=12 cmH2O. 3. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%. 4. Inspiratory flow trigger = 2 l/min or according to the practice of each institution; 5. fastest pressurization time; 6. expiratory trigger: 10-50% of the maximum inspiratory flow, eventually modified to avoid double triggering; 7. maximum inspiratory time 1.2 second. |
| Helmet continuous airway pressure (CPAP) | Experimental | Device: Noninvasive respiratory supportPatients in CPAP group will receive continuous helmet CPAP for at least 16 hours/day in the first 2 calendar days. Continuous CPAP without interruptions will be strongly encouraged in the first 48 hours of treatment. Dedicated helmets for noninvasive ventilation will be applied and size will be chosen according to patient's neck circumference. Treatment will be delivered through a high-flow generator. The following settings will be applied: 1. Continuous air flow>45 l/min. 2. Bi-tube circuit with no humidification, Y-piece with heat and moisture exchanger, or active heating and humidification with humidification chamber temperature set at 31 °C, 34 °C or 37 °C according to patients' comfort. 3. Expiratory positive end-expiratory pressure valve set to achieve PEEP=12 cmH2O. 4. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%. |
| High-flow nasal oxygen | Active comparator | Device: Noninvasive respiratory supportInitial set flow will be 50-60 l/min and flows will be decreased. in case of intolerance and/or according to patients' requirements: flows≥30 L/min will be mandatory in all enrolled patients. Humidification chamber will be set at 31 °C, 34 °C or 37 °C according to patient's comfort. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%. Weaning the patient from high-flow will be considered only after 48 hours from enrolment and will be discouraged until the patients is considered for ICU discharge. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Acute symptoms of respiratory failure PaO2/FiO2 ratio ≤ 200; PaCO2≤45mmHg; Absence of history of chronic respiratory failure or moderate to severe cardiac insufficiency (NYHA>2 or left ventricular ejection fraction<50%); Informed consent
- Patients that have already received NIV, CPAP continuously for more than 24 hours before the screening visit will be excluded.
- Pregnancy;
- Exacerbation of asthma or chronic obstructive pulmonary disease;
- Hypercapnia (PaCO2>45 mmHg) with or without respiratory acidosis;
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Noninvasive respiratory supportTreatment of acute hypoxemic respiratory failure | Device | Helmet Noninvasive ventilation (NIV), Helmet continuous airway pressure (CPAP), High-flow nasal oxygen |
Primary outcome
Rate of Endotracheal intubation
Time frame: 28 days
The proportion of patients requiring endotracheal intubation according to predefined criteria
11 secondary outcomes
Days free of invasive mechanical ventilation at day 28
Time frame: 28 days
Days free of invasive mechanical ventilation at day 60
Time frame: 60 days
Days free of invasive mechanical ventilation at day 90
Time frame: 90 days
Rate of In-intensive care unit mortality
Time frame: 90 days
Rate of In-hospital care unit mortality
Time frame: 90 days
Rate of 90-day mortality
Time frame: 90 days
90-day ICU free days
Time frame: 90 days
90-day hospital free days
Time frame: 90 days
Incidence of pneumonia
Time frame: 90 days
Incidence of shock
Time frame: 90 days
Incidence of barotrauma
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2025.
- Individual participant dataSharing planned: Yes. Individual data will be made available by the principal investigator upon a reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Domenico Luca Grieco, MD principal investigator
Fondazione Policlinico A. Gemelli IRCCS
Massimo Antonelli, MD study chair
Fondazione Policlinico A. Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Noninvasive respiratory support in people with Respiratory Failure and Hypoxemic Respiratory Failure, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Domenico Luca Grieco, MD (+393397681623, dlgrieco@outlook.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Endotracheal intubation (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.