Helmet NIV vs. CPAP vs. High-flow Nasal Oxygen in Hypoxemic Respiratory Failure (HENIVOT2)

September 29, 2025 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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;
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Helmet Noninvasive ventilation (NIV)

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.
Device: Noninvasive respiratory support
Treatment of acute hypoxemic respiratory failure
Experimental: Helmet continuous airway pressure (CPAP)

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%.
Device: Noninvasive respiratory support
Treatment of acute hypoxemic respiratory failure
Active Comparator: High-flow nasal oxygen

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.
Device: Noninvasive respiratory support
Treatment of acute hypoxemic respiratory failure

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of Endotracheal intubation
Time Frame: 28 days
The proportion of patients requiring endotracheal intubation according to predefined criteria
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Days free of invasive mechanical ventilation at day 28
Time Frame: 28 days
The number of days in which patients do not receive mechanical ventilation within 28 days from randomization
28 days
Days free of invasive mechanical ventilation at day 60
Time Frame: 60 days
The number of days in which patients do not receive mechanical ventilation within 60 days from randomization
60 days
Days free of invasive mechanical ventilation at day 90
Time Frame: 90 days
The number of days in which patients do not receive mechanical ventilation within 60 days from randomization
90 days
Rate of In-intensive care unit mortality
Time Frame: 90 days
All-cause mortality, assessed at the discharge from the intensive care unit
90 days
Rate of In-hospital care unit mortality
Time Frame: 90 days
All-cause mortality, assessed at the discharge from the hospital
90 days
Rate of 90-day mortality
Time Frame: 90 days
All-cause 90-day mortality
90 days
90-day ICU free days
Time Frame: 90 days
The days not spent in the intensive care unit by the patient on a 90-day basis
90 days
90-day hospital free days
Time Frame: 90 days
The days not spent in the hospital by the patient on a 90-day basis
90 days
Incidence of pneumonia
Time Frame: 90 days
Incidence of pneumonia, diagnosed after the treatment start and during the ICU stay
90 days
Incidence of shock
Time Frame: 90 days
Incidence of shock, diagnosed after treatment start and during the ICU stay
90 days
Incidence of barotrauma
Time Frame: 90 days
Incidence of barotrauma, defined as pneumothorax o pneumomediastinum after treatment start and during the ICU stay
90 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety endpoint-causes of endotracheal intubation
Time Frame: 28 days
Among patients meeting the primary endpoint, the cause of noninvasive treatment failure (as defined by the predefined intubation criteria)
28 days
Safety endpoint-time to treatment failure
Time Frame: 28 days
In patients meeting the primary endpoint, the time (hours) from randomization to intubation
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Catholic University of the Sacred Heart
Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Domenico Luca Grieco, MD, Fondazione Policlinico A. Gemelli IRCCS
  • Study Chair: Massimo Antonelli, MD, Fondazione Policlinico A. Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HENIVOT2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual data will be made available by the principal investigator upon a reasonable request

IPD Sharing Time Frame

With publication the results

IPD Sharing Access Criteria

Individual data will be made available by the principal investigator upon a reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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