## Protocol Section
### Identification Module
**NCT ID:** NCT02875379

**Brief Title:** Clinical Comparison of Different Humidification Strategies During Noninvasive Ventilation With Helmet

**Official Title:** Clinical Comparison of Different Humidification Strategies During Noninvasive Ventilation With Helmet

#### Organization Study ID Info
**ID:** 11491/15
#### Organization
**Class:** OTHER
**Full Name:** Catholic University of the Sacred Heart
### Status Module
#### Completion Date
**Date:** 2019-01-23

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-01-24

**Type:** ACTUAL

**Last Update Submit Date:** 2019-01-23

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2019-01-23

**Type:** ACTUAL

#### Start Date
**Date:** 2017-02-01

**Type:** ACTUAL

**Status Verified Date:** 2019-01

#### Study First Post Date
**Date:** 2016-08-23
**Type:** ESTIMATED
**Study First Submit Date:** 2015-07-27
**Study First Submit QC Date:** 2016-08-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Catholic University of the Sacred Heart

#### Responsible Party

**Investigator Affiliation:** Catholic University of the Sacred Heart

**Investigator Full Name:** Massimo Antonelli

**Investigator Title:** M.D. Full Professor of Anesthesiology and Intensive Care. Head of the department of Anesthesiology and Intensive Care medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Background. Non invasive positive pressure ventilation (NIV) is among first line treatments of acute respiratory failure. Several interfaces are available for non-invasive ventilation.Despite full face and oronasal masks are more frequently used, some evidence suggests that helmets may optimize patients' comfort and NIV tolerability.

During NIV, humidification strategies (heat and moisture exchangers HME or heated humidifiers HH) may significantly affect patient's comfort and work of breathing.

Despite physiological data suggested heated humidification as the best strategy during NIV with full face masks, no differences were found in a randomized controlled study assessing the effects of HME or HH on a pragmatic clinical outcome.

However, the higher dead space (i.e. 18 L/min) and rebreathing rate observed during helmet NIV make such results not applicable to this particular setting.

The investigators designed a randomized-crossover trial to assess the effect of four humidification strategies during helmet NIV on patients with acute respiratory failure, in terms of comfort, work of breathing and patient-ventilator interaction.

Methods. All awake, collaborative, hypoxemic patients requiring mechanical ventilation will be considered for the enrollment. Hypercapnic patients (i.e.PaCO2\>45 mmHg) will be excluded.

Each enrolled patient will undergo helmet NIV with all the following humidification strategies in a random order. Each period will last 60 minutes.

* Passive humidification, double tube circuit.
* Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 33°C.
* Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 37°C.
* Passive humidification with HME, Y-piece circuit.

Ventilatory settings (Draeger Evita xl or Evita infinity ventilators):

Pressure support ventilation; pressure support=20 cmH20; FiO2 titrated to obtain SpO2 between 92 and 98%; positive end-expiratory pressure=10 cmH2O; maximum inspiratory time 0.9 seconds; inspiratory flow trigger = 2 l/min; expiratory trigger: 30% of the maximum inspiratory flow; pressurization time=0,00 s.

Such settings will be kept unchanged during the whole study period. An oesophageal catheter will be placed and secured to measure oesophageal pressure (Pes) and gastric pressure (Pga) (Nutrivent, Italy): the reliability of the measured pressure will be confirmed with an airway occlusion test during NIV with oronasal mask. Work of breathing will be estimated with the pressure-time product (PTP) of the pleural pressure.

A pneumotachograph (KleisTek) will record flow, airway pressure, Pes and Pga on a dedicated laptop.

At the end of each cycle, the patient will be asked to rate his/her discomfort on a visual analog scale (VAS) modified for ICU patients. The level of dyspnea will be assessed with the Borg dyspnea scale.

The following parameters will be record at the end of each cycle:

Arterial pressure, heart rate, respiratory rate, SpO2, pH, PCO2, PaO2, SaO2. Airway and esophageal pressure signals will be reviewed offline to detect patient-ventilator asynchronies (ineffective efforts, double cycling, premature cycling, delayed cycling) and asynchrony index (number of asynchrony events divided by the total respiratory rate computed as the sum of the number of ventilator cycles (triggered or not) and of wasted efforts) will be computed. The trigger delay will be also measured. The pressurization and depressurization velocity will be assessed with the PTP airway index 300 and 500 (inspiratory and expiratory), as suggested by Ferrone and coworkers. The work of breathing (WOB) for each breath will be estimated by PTPes.

An hygrometer (Dimar SRL, Italy) will measure and record on a dedicated laptop Helmet temperature, relative and absolute humidity.

Primary endpoints: patient's comfort, work of breathing and asynchrony index.

Sample Sizing:

Given the physiological design of the study, the investigators did not make an a priori sample size and plan to enroll 24 patients.

**Detailed Description:** Background Non invasive positive pressure ventilation (NIV) is among first line treatments of acute respiratory failure. In patients with new-onset respiratory failure, NIV was showed to reduce the rate of complications and the length of ICU stay, as compared to invasive mechanical ventilation\[1\] Several interfaces are available for non-invasive ventilation: full face masks, oronasal masks, nasal prongs and helmets\[2\].

Despite full face and oronasal masks are more frequently used, some evidence suggests that helmets may optimize patients' comfort and NIV tolerability. The helmet allows patients' interaction, speech, feeding and does not limit cough. In addition, skin necrosis, gastric distension, or eye irritation are seldom observed during helmet NIV, while may be consequences of long-term treatments with face masks. \[3\] On the contrary, helmet NIV hampers tidal volume monitoring, is contraindicated in hypercapnic patients and requires specific ventilator settings\[4\]. Lastly, when compared to face masks, helmets may increase the work of breathing and worsen patient-ventilator interaction\[5\]\[6\]\[7\].

During NIV, humidification strategies (heat and moisture exchangers HME or heated humidifiers HH) may significantly affect patient's comfort and work of breathing \[8\]\[9\].

Despite physiological data suggested heated humidification as the best strategy during NIV with full face masks\[8\]\[9\], no differences were found in a randomized controlled study assessing the effects of HME or HH on a pragmatic clinical outcome\[10\].

However, the higher dead space (i.e. 18 L/min) and rebreathing rate observed during helmet NIV make such results not applicable to this particular setting.

One only study assessed the effects of a HH during helmet low-flow continuous positive airway pressure on comfort in healthy volunteers\[11\]. Indeed, patients suffering from acute respiratory failure may behave differently, especially in terms of minute ventilation and maximum inspiratory flow.

A recent bench study identified a better patient-ventilator interaction when helmet NIV was provided through a double tube circuit, as compared to the Y-piece system \[12\]. The investigators designed a randomized-crossover trial to assess the effect of four humidification strategies during helmet NIV on patients with acute respiratory failure, in terms of comfort, work of breathing and patient-ventilator interaction.

Methods Design: monocentric, randomized, cross-over trial. Each enrolled patient will undergo helmet NIV with all the following humidification strategies in a random order. Each period will last 60 minutes.

* Passive humidification, double tube circuit.
* Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 33°C.
* Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 37°C.
* Passive humidification with HME, Y-piece circuit.

Ventilatory settings (Draeger Evita xl or Evita infinity ventilators):

Pressure support ventilation; pressure support=20 cmH20\[4\]; FiO2 titrated to obtain SpO2 between 92 and 98%; positive end-expiratory pressure=10 cmH2O\[4\]; maximum inspiratory time 0.9 seconds; inspiratory flow trigger = 2 l/min; expiratory trigger: 30% of the maximum inspiratory flow; pressurization time=0,00 s.

Such settings will be kept unchanged during the whole study period. An oesophageal catheter will be placed and secured to measure oesophageal pressure (Pes) and gastric pressure (Pga) (Nutrivent, Italy): the reliability of the measured pressure will be confirmed with an airway occlusion test during NIV with oronasal mask\[13\]. Work of breathing will be estimated with the pressure-time product (PTP) of the pleural pressure\[13\].

A pneumotachograph (KleisTek) will record flow, airway pressure, Pes and Pga on a dedicated laptop.

At the end of each cycle, the patient will be asked to rate his/her discomfort on a visual analog scale (VAS) modified for ICU patients. The level of dyspnea will be assessed with the Borg dyspnea scale\[14\].

The following parameters will be record at the end of each cycle:

Arterial pressure, heart rate, respiratory rate, SpO2, pH, PCO2, PaO2, SaO2. Airway and esophageal pressure signals will be reviewed offline to detect patient-ventilator asynchronies (ineffective efforts, double cycling, premature cycling, delayed cycling) and asynchrony index (number of asynchrony events divided by the total respiratory rate computed as the sum of the number of ventilator cycles (triggered or not) and of wasted efforts) will be computed\[15\]. The trigger delay will be also measured. The pressurization and depressurization velocity will be assessed with the PTP airway index 300 and 500 (inspiratory and expiratory), as suggested by Ferrone and coworkers\[12\]. The work of breathing (WOB) for each breath will be estimated by PTPes.

An hygrometer (Dimar SRL, Italy) will measure and record on a dedicated laptop Helmet temperature, relative and absolute humidity.

End point:

Primary endpoints: patient's comfort, work of breathing and asynchrony index.

Sample Sizing:

Given the physiological design of the study, the investigators did not make an a priori sample size and planned to enroll 24 patients.

Statistical analysis Qualitative data will be expressed as number of events (%) and continuous data as mean ± standard deviation or median \[Interquartile range\]. Comparisons concerning qualitative variables will be performed with the Mc-Namar test. Ordinal qualitative variables or non normal quantitative variables will be compared with the Friedman's Test, the wilcoxon sum of ranks test or the Mann-Whitney test, as appropriate. All analysis will be performed applying a bilateral hypothesis. P ≤ 0.05 will be considered significant. Statistical analysis will be performed with SPSS 20.0.

### Conditions Module

**Conditions:**

- Respiratory Failure

**Keywords:**

- Noninvasive Ventilation

- Mechanical Ventilation

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Passive humidification with heat and moisture exchanger, Y-piece circuit.

**Intervention Names:**

- Procedure: Measurements

**Label:** HME

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 33°C.

**Intervention Names:**

- Procedure: Measurements

**Label:** HH33

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Heated humification (MR 730, Fisher \& Paykel, Auckland, New Zealand), humidification chamber temperature 33°C.

**Intervention Names:**

- Procedure: Measurements

**Label:** HH37

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Passive humidification, double tube circuit

**Intervention Names:**

- Procedure: Measurements

**Label:** NoH

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HH33

- HH37

- HME

- NoH

**Description:** Measurements of respiratory mechanics and parameters, arterial blood gases and comfort

**Name:** Measurements

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Patient's comfort, assessed by visual analogic scale modified for ICU patients

**Measure:** Comfort assessed by visual analogic scale modified for ICU patients

**Time Frame:** At the end of each 1-hour ventilation period

**Description:** Asynchrony index number of asynchrony events divided by the total respiratory rate computed as the sum of the number of ventilator cycles (triggered or not) and of wasted efforts. Inspiratory trigger delay (time between the onset of patient's effort and ventilatory support). Pressurization and depressurization efficacy.

**Measure:** Patient-ventilator asynchrony. Asynchrony index

**Time Frame:** At the end of each 1-hour ventilation period

**Description:** Pressure time product of the esophageal pressure (PTPes) and pressure time product of the transdiaphragmatic pressure (PTPdi)

**Measure:** Work of breathing. Oesophageal pressure time product

**Time Frame:** At the end of each 1-hour ventilation period

#### Secondary Outcomes

**Measure:** PaO2

**Time Frame:** At the end of each 1-hour ventilation period

**Measure:** respiratory rate

**Time Frame:** At the end of each 1-hour ventilation period

**Description:** Borg dyspnea score

**Measure:** Dyspnea

**Time Frame:** At the end of each 1-hour ventilation period

**Measure:** Helmet humidity

**Time Frame:** At the end of each 1-hour ventilation period

**Measure:** Helmet temperature

**Time Frame:** At the end of each 1-hour ventilation period

**Measure:** PaCO2

**Time Frame:** At the end of each 1-hour ventilation period

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Awake and collaborative patients
* Age\>18 years
* Need for noninvasive mechanical ventilation
* Informed consent

Exclusion Criteria:

* Cardiopulmonary resuscitation
* Haemodynamic instability
* Coma
* Asma
* Hypercapnia (paCO2\>45 mmHg)
* Recent gastric or abdominal surgery

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Rome

**Country:** Italy

**Facility:** General ICU, A. Gemelli hospital

**Zip:** 00100

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Bongiovanni F, Grieco DL, Anzellotti GM, Menga LS, Michi T, Cesarano M, Raggi V, De Bartolomeo C, Mura B, Mercurio G, D'Arrigo S, Bello G, Maviglia R, Pennisi MA, Antonelli M. Gas conditioning during helmet noninvasive ventilation: effect on comfort, gas exchange, inspiratory effort, transpulmonary pressure and patient-ventilator interaction. Ann Intensive Care. 2021 Dec 24;11(1):184. doi: 10.1186/s13613-021-00972-9.

**PMID:** 34952962

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012120

- Term: Respiration Disorders

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M14968

- Name: Respiratory Insufficiency

- Relevance: HIGH

- As Found: Respiratory Failure

- ID: M14957

- Name: Respiration Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012131

- Term: Respiratory Insufficiency

### Misc Info Module

- Version Holder: 2024-05-24
