OptiTHO: Early Non-invasive Ventilation and High-flow Nasal Oxygen Therapy for Preventing Delayed Respiratory Failure in Hypoxemic Blunt Chest Trauma Patients.

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT03943914

Collaborator

(none)

144

Enrollment

Locations

Arms

25.5

Actual Duration (Months)

10.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In blunt chest trauma patients without immediate life-threatening conditions, delayed respiratory failure and need for mechanical ventilation may still occur in 12 to 40% of patients, depending on the severity of the trauma, the preexisting conditions and the intensity of initial management.

In this context, non-invasive ventilation (NIV) is recommended in hypoxemic chest trauma patients, defined as a PaO2/FiO2 ratio < 200 mmHg. However, there is a large heterogeneity among studies regarding the severity of injuries, the degree of hypoxemia and the timing of enrollment. The interest of a preventive strategy during the early phase of blunt chest trauma, before the occurrence of respiratory distress or severe hypoxemia, is not formally established in the literature. Moreover, high-flow nasal oxygen therapy (HFNC-O2) appears to be a reliable and better tolerated alternative to conventional oxygen therapy (COT), associated with a significant reduction in intubation rate in hypoxemic patients.

Two NIV strategies are compared:

In the experimental strategy, NIV is performed after inclusion in patients with moderate hypoxemia, defined by a PaO2/FiO2 ratio < 300 mmHg. The minimally required duration of NIV was 4 hours per day for at least 2 calendar days.
In the control group, patients receive oxygen from nasal cannula or high concentration oxygen mask according to the FiO2 needed to achieve SpO2 > 92%. NIV is initiated only in patients having PaO2/FiO2 ratio < 200 mmHg under COT.

Investigators hypothesized that an early strategy associating HFNC-O2 and preventive NIV in hypoxemic blunt chest trauma patients may reduce the need for mechanical ventilation compared to the recommended strategy associating COT and late NIV.

Condition or Disease	Intervention/Treatment	Phase
Chest Injuries Respiratory Failure	Combination Product: Preventive strategy Combination Product: Standard of care	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Early Non-invasive Ventilation and High-flow Nasal Oxygen Therapy for Preventing Delayed Respiratory Failure in Hypoxemic Blunt Chest Trauma Patients.

Actual Study Start Date :

Sep 25, 2019

Actual Primary Completion Date :

Nov 9, 2021

Actual Study Completion Date :

Nov 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: An "early" NIV strategy associated with HFNC-O2	Combination Product: Preventive strategy In the experimental strategy, NIV is performed after inclusion in patients with moderate hypoxemia, defined by a PaO2/FiO2 ratio < 300 mmHg. The minimally required duration of NIV was 4 hours per day for at least 2 calendar days. The daily duration of NIV can be increased at the discretion of the physician in patients with signs of delayed respiratory failure under HFNC-O2 and improving under NIV. Beyond the first 48 hours, NIV and HFNC-O2 can be stopped and the patient switched to COT if respiratory rate < 25/min and SpO2 > 92% under FiO2 < 30% for at least 6 hours.
Active Comparator: A "late" NIV strategy associated with COT	Combination Product: Standard of care In the control group, patients receive oxygen from nasal cannula or high concentration oxygen mask according to the FiO2 needed to achieve SpO2 > 92%. NIV is initiated only in patients having PaO2/FiO2 ratio < 200 mmHg under COT. A trial of curative NIV is allowed at the discretion of the physician in patients who have signs of delayed respiratory failure and no other organ dysfunction. The non-improvement of respiratory conditions after 1 hour of NIV, the NIV-dependence (≥ 12 consecutive hours) or NIV-intolerance should be considered as criteria for endotracheal intubation.

Arm

Intervention/Treatment

Experimental: An "early" NIV strategy associated with HFNC-O2

Combination Product: Preventive strategy

In the experimental strategy, NIV is performed after inclusion in patients with moderate hypoxemia, defined by a PaO2/FiO2 ratio < 300 mmHg. The minimally required duration of NIV was 4 hours per day for at least 2 calendar days. The daily duration of NIV can be increased at the discretion of the physician in patients with signs of delayed respiratory failure under HFNC-O2 and improving under NIV. Beyond the first 48 hours, NIV and HFNC-O2 can be stopped and the patient switched to COT if respiratory rate < 25/min and SpO2 > 92% under FiO2 < 30% for at least 6 hours.

Active Comparator: A "late" NIV strategy associated with COT

Combination Product: Standard of care

In the control group, patients receive oxygen from nasal cannula or high concentration oxygen mask according to the FiO2 needed to achieve SpO2 > 92%. NIV is initiated only in patients having PaO2/FiO2 ratio < 200 mmHg under COT. A trial of curative NIV is allowed at the discretion of the physician in patients who have signs of delayed respiratory failure and no other organ dysfunction. The non-improvement of respiratory conditions after 1 hour of NIV, the NIV-dependence (≥ 12 consecutive hours) or NIV-intolerance should be considered as criteria for endotracheal intubation.

Outcome Measures

Primary Outcome Measures

Necessity to perform endotracheal intubation [Up to 14 days after randomization]
To ensure the consistency of indications across sites and reduce the risk of delayed intubation, the following criteria for endotracheal intubation must be used (only one criterion is needed): cardiac arrest or significant hemodynamic instability, deterioration of neurologic status, signs of persisting or worsening respiratory failure as defined by at least two of the following criteria: respiratory rate of more than 35 breaths per minute, lack of improvement in signs of high respiratory-muscle workload, development of copious tracheal secretions, signs of respiratory exhaustion (pH <7.32 or PaCO2 > 50 mmHg), major hypoxemia (PaO2/FiO2 ratio <100 or SpO2 <92% for more than 5 minutes).

Secondary Outcome Measures

PaO2/FiO2 ratio [every 6 hours during the first 48 hours after randomization]
Respiratory rate [every 6 hours during the first 48 hours after randomization]
Dyspnea score [every 6 hours during the first 48 hours after randomization]
Dyspnea score : +2 = significant improvement; +1 = slight improvement; 0 = no change; -1 = slight deterioration ; -2 = significant deterioration
ICU and hospital length of stay [Up to 14 days after randomization]
ICU or in-hospital mortality [Up to 14 days after randomization]
Number of ventilator free-days [Up to 14 days after randomization]
Days alive and without invasive or non-invasive mechanical ventilation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient admitted in intensive care unit within 48 hours after a high-risk blunt chest trauma, defined by a TTS (Thorax Trauma Severity) score ≥ 8.
Hypoxemia defined by a PaO2/FiO2 ratio < 300, and the absence of hypercapnia (PaCO2 < 45 mmHg).
Without indication of endotracheal intubation at inclusion.
Affiliated person or beneficiary of a social security scheme.
Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

Criteria relating to formal indication to NIV: Exacerbation of underlying chronic respiratory disease, cardiogenic pulmonary edema, severe neutropenia.
Criteria relating to contraindications to NIV: Hemodynamic instability, Glasgow Coma Scale score ≤ 12 or excessive agitation, or other contraindications to non-invasive ventilation (active gastrointestinal bleeding, low level of consciousness, multiorgan failure, airway patency problems, lack of cooperation or hemodynamic instability).
Associated traumatic lesions entailing particular risks: severe brain injury, complex facial trauma, tetraplegia, tracheobronchial or esophageal injuries, thoracic or abdominal trauma with indication for surgery by thoracotomy or laparotomy.
Criteria relating to the regulation: A do-not-intubate order and a decision not to participate, persons placed under judicial protection, persons participating in another research including a period of exclusion still in course, severely altered physical and/or psychological health which, according to the investigator, could affect the participant's compliance of the study.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Amiens-Picardie	Amiens	France	80054
2	CH d'Annecy	Annecy	France
3	CHU de Bordeaux	Bordeaux	France	33076
4	CHU de Clermont-Ferrand	Clermont-Ferrand	France	63003
5	APHP - Hôpital Beaujon	Clichy	France	92110
6	AP-HM - Hôpital de la Timone	Marseille	France	13385
7	CHU de Nîmes	Nîmes	France	30029
8	CH de Pau	Pau	France	64000
9	HCL - Hôpital Lyon Sud	Pierre-Bénite	France	69495
10	CHU de Poitiers	Poitiers	France	86021
11	CHU de Saint Etienne	Saint-Priest-en-Jarez	France	42270
12	CHU de Strasbourg - Hôpital Civil	Strasbourg	France	67091
13	CHU de Strasbourg -Hôpital de Hautepierre	Strasbourg	France	67200
14	Hôpital Robert Picqué	Villenave-d'Ornon	France	33882