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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure With Hypoxia
• Intervention / Treatment: Device: Noninvasive respiratory support

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy
    • Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna
  • Chieti, Italy
    • SS. Annunziata Hospital, Gabriele d'Annunzio University of Chieti-Pescara
  • Ferrara, Italy
    • Azienda Ospedaliera-Universitaria Arcispedale Sant'Anna, University of Ferrara
  • Rimini, Italy
    • Infermi Hospital
  • Rome, Italy
    • Fondazione Policlinico Universitaro A. Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High-flow nasal cannula; 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; 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
Experimental: Helmet noninvasive ventilation; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva; Università degli studi di Chieti
• Investigators: Study Director: Massimo Antonelli, MD, Fondazione Policlinico A. Gemelli IRCCS; Principal Investigator: Domenico Luca Grieco, MD, Fondazione Policlinico A. Gemelli IRCCS

Publications and helpful links

General Publications

• Grieco DL, Menga LS, Cesarano M, Rosa T, Spadaro S, Bitondo MM, Montomoli J, Falo G, Tonetti T, Cutuli SL, Pintaudi G, Tanzarella ES, Piervincenzi E, Bongiovanni F, Dell'Anna AM, Delle Cese L, Berardi C, Carelli S, Bocci MG, Montini L, Bello G, Natalini D, De Pascale G, Velardo M, Volta CA, Ranieri VM, Conti G, Maggiore SM, Antonelli M; COVID-ICU Gemelli Study Group. Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1731-1743. doi: 10.1001/jama.2021.4682.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Actual): January 10, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia
• Other Study ID Numbers: 4443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be made available upon a reasonable request

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