Helmet Noninvasive Ventilation vs. High-flow Nasal Cannula in Moderate-to-severe Acute Hypoxemic Respiratory Failure

Study Overview
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Brief Summary
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Helmet noninvasive ventilation and high-flow nasal cannula are novel tools for the first-line treatment of acute hypoxemic respiratory failure. Compared to face-mask noninvasive ventilation in randomized trials, both have improved clinical outcome of patients with moderate-to-severe hypoxemic respiratory failure. As compared to high-flow nasal cannula, helmet noninvasive ventilation improves oxygenation, reduces inspiratory effort, respiratory rate and dyspnea. Whether these physiological benefits are translated into improved outcome remains to be established. The investigators designed a randomized trial to establish whether first line treatment with Helmet noninvasive ventilation is capable of increasing the number of 28-day respiratory-support-free days, as compared to high-flow nasal cannula in patients with moderate-to-severe acute hypoxemic respiratory failure.

Official Title
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Helmet Noninvasive Ventilation vs. High-flow Nasal Cannula in Moderate-to-severe Acute Hypoxemic Respiratory Failure: an Open Label, Pilot, Randomized Trial

Conditions
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Respiratory Failure With Hypoxia

Intervention / Treatment
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* Device: Noninvasive respiratory support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute-onset respiratory distress or flue-related symptoms Moderate-to-severe hypoxemia (PaO2/FiO2<=200 mmHg) PaCO2<45 mmHg pH>7.30 Exclusion Criteria: Need for urgent endo-tracheal intubation Exacerbation of asthma or chronic obstructive pulmonary disease Documented pneumothorax Clinical diagnosis of Cardiogenic pulmonary oedema Do-not-intubate order Altered neurological status that requires immediate intubation and/or making the patient uncooperative Thoracic or abdominal surgery in the previous 7 days Recent head surgery or anatomy that prevent the application of helmet or Optiflow to patient's face

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-flow nasal cannula<br>High-flow nasal cannula will be delivered with the Optiflow system. Initial set flow will be ≥ 50 /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 (MR860, Fisher and Paykel healthcare, New Zealand) will be set at 37 °C or 34 °C according to patient's comfort. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%. The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. Weaning from high-flow will be considered as standardized criteria are met. | Device: Noninvasive respiratory support<br>* In both arms, the treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. Patients will have to undergo the allocated treatment within 1 hour from the moment of randomization and within 24 hours from admission in the intensive care unit<br>|
| Experimental: Helmet noninvasive ventilation<br>Patients will receive continuous helmet pressure support ventilation for at least 16 hours/day the first 2 calendar days. Continuous noninvasive ventilation without interruptions will be strongly encouraged in the first 24 hours of treatment. The ventilator will be set in pressure support mode. Use of continuous positive airway pressure by flow generators and Venturi systems instead of pressure support ventilation will be allowed in case of shortage of ventilators. Maintenance of positive end-expiratory pressure ≥ 8-10 during the treatment is mandatory. After weaning and during any interruption from noninvasive ventilation, patients will undergo low-flow or high-flow oxygen, according to the decision of the attending physician. The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. | Device: Noninvasive respiratory support<br>* In both arms, the treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. Patients will have to undergo the allocated treatment within 1 hour from the moment of randomization and within 24 hours from admission in the intensive care unit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory-support free days within 28 days from randomization | The number of days in which patients did not receive any form of respiratory support (i.e. high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotracheal intubation | The proportion of patients requiring endotracheal intubation in the two groups. The need for endotracheal intubation will be established with predefined criteria, which will be evaluated a posteriori by an independent adjudication committee | 28 days | 
| Invasive ventilation-free days within 28 days from randomization | The number of days in which patients did not receive invasive mechanical ventilation | 28 days | 
| Invasive ventilation-free days within 60 days from randomization | The number of days in which patients did not receive invasive mechanical ventilation | 60 days | 
| Oxygenation | The ratio of PaO2 to FiO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge | 28 days | 
| Carbon dioxide | PaCO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge | 28 days | 
| Dyspnea | Dyspnea will be evaluated through a visual analog scale (0-10, where 10 represents the most sever symptom) will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge | 28 days | 
| Respiratory rate | Respiratory rate will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge | 28 days | 
| In-intensive care unit mortality | Clinical outcome (dead/alive) at intensive care unit discharge | 90 days | 
| In-hospital mortality | Clinical outcome (dead/alive) at hospital discharge | 90 days | 
| 90-day mortality | Clinical outcome (dead/alive) at 90 days after randomization | 90 days | 
| Quality of life after recovery | Quality of life in survivors, assessed by Short Form-36 questionnaire | 1 year |