Efficacy of High Flow Nasal Oxygen Therapy Started in the Emergency Room Versus Conventional Oxygen Therapy in Patients With Acute Hypoxemic Respiratory Distress (HIFLOWED)

• ClinicalTrials.gov Identifier: NCT04607967
• Recruitment Status: Not yet recruiting
• First Posted: October 29, 2020
• Last Update Posted: October 29, 2020
• Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: Centre Hospitalier Universitaire Dijon; centre Hospitalier Intercommunal de Vesoul; Centre Hospitalier Universitaire de Saint Louis APHP; Poitiers University Hospital
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Besancon

Study Description

Brief Summary:

A quarter of the patients admitted to the Shock Room or Resuscitation Room of an Emergency Department (ED) are admitted for severe hypoxemia resulting from acute respiratory distress. Like all life-threatening conditions, acute respiratory distress (ARD) requires a rapid identification and prompt implementation of effective resuscitation measures.

Oxygen treatment, first described in 1890, remains one of the most important discoveries in medicine. The purpose of oxygenation is to alleviate respiratory failure and to restore a satisfactory hematosis. The choice of the oxygen delivery device is based on the severity of the hypoxemia, the underlying physiological problems, the type of dyspnea and the patient's tolerance to the device. The most commonly used devices are nasal cannula, face mask and high-concentration face mask (conventional oxygen therapy). High Flow Nasal Oxygen (HFNO) is now widely used as a complement to conventional oxygen therapy in the EDs.

HFNO ensures good clinical tolerance and better patient comfort (humidification and heating of inhaled gases, ease of speech and possible oral feeding) than the other oxygen devices. The HFNO flow rate can go up to 60-70 L/min with an FIO2 of 100% compared to a maximum output of 15 L/min with conventional oxygen-therapy.

Given the lack of data and clinical trials concerning the systematic use of HFNO in EDs in cases of severe hypoxemia, a prospective study is essential. The purpose of this work is to evaluate the contribution of early administration of HFNO for patients with acute non-hypercapnic respiratory distress presenting in the ED, with the aim of obtaining rapid correction of hematosis. The objective of this work is to compare Conventional Oxygen Therapy (CO) delivered by nasal cannula or nasal-oral mask at flow rates up to a maximum of 15 liters, to HFNO with the hypothesis that HFNO would reduce the need for ventilation therapy escalation. The other hypotheses concern the interest of the HFNO in reducing the use of intensive care hospitalization and thus the costs of treating these patients.

Condition or disease	Intervention/treatment	Phase
Acute Hypoxemic Respiratory Distress	Device: High Flow Nasal Oxygen	Not Applicable

Detailed Description:

Acute Respiratory Distress (ARD) is defined as the inability of a patient to maintain normal hematosis. A hematosis disorder is defined as an alteration of the blood gases with hypoxemia (partial pressure of oxygen (PaO2) less than 80 mm of mercury (mmHg) and transcutaneous O2 saturation (SpO2) less than 95%), associated or not with hypercapnia (partial pressure of carbon dioxide (PaCO2) > 45 mmHg) or hypocapnia depending on the cause of the acute respiratory failure. Compensation mechanisms include increased minute ventilation, increased ventilatory work and increased cardiac output. When these compensatory mechanisms are insufficient, acute respiratory distress occurs, along with signs of heart failure (acute cor pulmonale) and neuropsychic disorders.

Without care, a potentially fatal respiratory decompensation may occur. ARD can be hypercapnic. It's defined by a PaCO2 greater than 45 mm Hg associated with a drop in blood pH reflecting respiratory acidosis. Hypoxemic ARD is defined by a PaO2 of less than 60 mm Hg.

A quarter of the patients admitted to the Vital Emergency Room (VER) are admitted for severe hypoxemia resulting from acute respiratory distress.

Like all life-threatening conditions, acute respiratory distress (ARD) requires a rapid identification and prompt implementation of effective resuscitation measures.

Oxygen treatment, first described in 1890, remains one of the most important discoveries in medicine. The purpose of oxygenation is to alleviate respiratory failure and to restore a satisfactory hematosis. Most experts stress the importance of having an SpO2 target of more than 90% in the majority of patients. While non-invasive ventilation (NIV) is the standard of care in the initial management of patients with hypercapnic acidosis, there are currently no recommendations for oxygen therapy in patients with acute hypoxic respiratory distress in the emergency department.

The choice of the oxygen delivery device is based on the severity of the hypoxemia, the underlying physiological problems, the type of dyspnea and the patient's tolerance to the device. The most commonly used devices are nasal cannula, face mask and high-concentration face mask. They offer several Oxygen Inspired Fraction (fraction of O2 in the gas mixture breathed, FiO2) depending on the oxygen flow rate instituted.

High Flow Nasal Oxygen (HFNO) is used as a complement to conventional oxygen therapy in emergency departments in general and in particular in the different emergency departments participating in our study. HFNO is used in hypoxemic respiratory insufficiency according to the national and international recommendations.

HFNO makes it possible to administer a much higher flow of oxygen than with the usual hospital and prehospital flow meters. This flow rate can go up to 60-70 L/min with an FIO2 of 100%. This high flow rate allows to generate low levels of positive pressure in the upper airways and to adapt the FIO2 delivered up to 100% notably thanks to dedicated nasal cannulas. HFNO ensures good clinical tolerance and better patient comfort (humidification and heating of inhaled gases, ease of speech and possible oral feeding) than the other oxygen devices. Its use was initially developed in paediatric and neonatal intensive care units. It was then gradually extended to "adult" intensive care units and intensive care units in the treatment of hypoxemic, non-hypercapnic acute respiratory failure (ARF) with no indication for orotracheal intubation. The FLORALI study confirms its use as an alternative to conventional oxygen therapy in intensive care units. Its implementation, its efficacy (improvement of dyspnea, clinical respiratory signs and oxygenation parameters), its good tolerance and acceptability by the nursing staff, were recently demonstrated in an emergency department in 17 patients with hypoxic respiratory insufficiency. However, despite the increasing number of studies, methodologically heterogeneous and of insufficient statistical power carried out on HFNO, these studies remain non-contributory with regard to the superiority of high nasal flow compared to conventional oxygen therapy. The gain of the HFNO strategy seems to be established for clinical ventilatory parameters and dyspnea level. However, the need for therapeutic escalation and mortality have not been precisely evaluated. On the other hand, there is very little information on the time required for the implementation of HFNO in the various studies carried out in patients. The available data indicate that the average time would usually be more than 90 minutes.

Given the lack of data and clinical trials concerning the systematic use of HFNO in emergency departments in cases of severe hypoxemia, a prospective study is essential. The purpose of this work is to evaluate the contribution of early administration of HFNO for patients with acute non-hypercapnic respiratory distress presenting in the emergency department, with the aim of obtaining rapid correction of hematosis. The objective of this work is to compare Conventional Oxygen Therapy (CO) delivered by nasal cannula or nasal-oral mask at flow rates up to a maximum of 15 liters to HFNO, with the hypothesis that HFNO would reduce the need for ventilation therapy escalation. The other hypotheses concern the interest of the HFNO in reducing the use of intensive care hospitalization and thus the costs of treating these patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of High Flow Nasal Oxygen Therapy Started in the Emergency Room Versus Conventional Oxygen Therapy in Patients With Acute Hypoxemic Respiratory Distress
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: July 1, 2022
• Estimated Study Completion Date: January 1, 2024

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Conventional oxygen-therapy (study group "CO"); Patients randomized in the "Coventional Oxygen" group will be treated according to the national and international recommandations with a conventional oxygen-therapy device (nasal cannula or nasal-oral mask). Treatment failure will be evaluated after 4 hours by the need for a therapeutic escalation.
Experimental: High Flow Nasal Oxygen (study group "HNFO"); Patients randomized in the "HNFO" group will be treated according to the CE Certification with the high flow nasal oxygen device. Treatment failure will be evaluated after 4 hours by the need for a therapeutic escalation.	Device: High Flow Nasal Oxygen; Study participants are suffering from an acute hypoxemic respiratory distress. They have to be treated with oxygen-therapy that could be administered using a conventional oxygen device (study group "CO") or High Flow Nasal Oxygen (study group "HNFO"). During the first 30 minutes following patients admission, patients will be randomized to one of the two study groups. In both groups, the failure of the treatment will be evaluated by the need for a therapeutic escalation fours hours after the treatment initiation.; Other Name: HNFO

Outcome Measures

Primary Outcome Measures :

1. Therapeutic escalation [ Time Frame: 4 hours after treatment initiation ]
   The need for a therapeutic escalation will be searched 4 hours after treatment initiation (either Conventional Oxygen or High Flow Nasal Oxygen)

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients over 18 years of age
• Admitted to the Emergency Department for acute respiratory distress :
• FR ≥ at 25 cycles/min.
• And SpO2 < 90% in ambient air or ≤ at 92% under oxygen whatever the mode.
• And clinical signs of respiratory distress (pulling, thoraco-abdominal swinging).
• And PaO2/FIO2 ratio < 300mmHg.

Exclusion Criteria:

• Hypercapnic patients (PaCO2 > 45mmHg) with respiratory acidosis (pH<7.30).
• Indication for non-invasive ventilation or early invasive mechanical ventilation according to current scientific recommendations (acute pulmonary edema, COPD decompensation, or others).
• Dyspnea of traumatic origin.
• Traumatic pneumothorax.
• Hemodynamic instability (PAM<65mmHg).
• Patients treated with SMUR (Service Mobile d'Urgence et Réanimation - Mobile Emergency and Resuscitation Service) who have already received cardiac or pulmonary treatment.
• Patients with cognitive deterioration (Glasgow score less than 13, dementia or mental failure that would prevent good cooperation).
• Patients with lesion(s) of the oro-nasal sphere contraindicated for the implementation of High Flow Nasal Oxygen Therapy.
• Subject unlikely to cooperate in the study and/or low cooperation anticipated by the investigator.
• Subject without health insurance.
• Pregnant woman.
• Subject being in the exclusion period of another study or included in the "national volunteer file".

Contacts and Locations

Contacts

Contact: Abdo Khoury, MD; 33 3 81 66 88 36; akhoury@chu-besancon.fr

Contact: Jean-Baptiste Pretalli, PhD; 33 3 81 21 81 27; jbpretalli@chu-besancon.fr

Sponsors and Collaborators

Centre Hospitalier Universitaire de Besancon

Centre Hospitalier Universitaire Dijon

centre Hospitalier Intercommunal de Vesoul

Centre Hospitalier Universitaire de Saint Louis APHP

Poitiers University Hospital

More Information

• Responsible Party: Centre Hospitalier Universitaire de Besancon
• ClinicalTrials.gov Identifier: NCT04607967
• Other Study ID Numbers: 2020/472
• First Posted: October 29, 2020
• Last Update Posted: October 29, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Emergencies; Disease Attributes; Pathologic Processes