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

• ClinicalTrials.gov Identifier: NCT03943914
• Recruitment Status: Completed
• First Posted: May 9, 2019
• Last Update Posted: January 5, 2022
• Sponsor: University Hospital, Bordeaux
• Information provided by (Responsible Party): University Hospital, Bordeaux

Tracking Information

• First Submitted Date: May 7, 2019
• First Posted Date: May 9, 2019
• Last Update Posted Date: January 5, 2022
• Actual Study Start Date: September 25, 2019
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2019)

Necessity to perform endotracheal intubation [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 7, 2019)

• PaO2/FiO2 ratio [ Time Frame: every 6 hours during the first 48 hours after randomization ]
• Respiratory rate [ Time Frame: every 6 hours during the first 48 hours after randomization ]
• Dyspnea score [ Time Frame: 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 [ Time Frame: Up to 14 days after randomization ]
• ICU or in-hospital mortality [ Time Frame: Up to 14 days after randomization ]
• Number of ventilator free-days [ Time Frame: Up to 14 days after randomization ]
  Days alive and without invasive or non-invasive mechanical ventilation

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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:

1. 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.
2. 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Chest Injuries
• Respiratory Failure

Intervention

• 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.
• 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.

Study Arms

• Experimental: An "early" NIV strategy associated with HFNC-O2
  Intervention: Combination Product: Preventive strategy
• Active Comparator: A "late" NIV strategy associated with COT
  Intervention: Combination Product: Standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 4, 2022): 144
• Original Estimated Enrollment (submitted: May 7, 2019): 278
• Actual Study Completion Date: November 9, 2021
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03943914
• Other Study ID Numbers: CHUBX 2018/62
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Bordeaux
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Bordeaux
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Antoine BENARD, MD; Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique (USMR) du CHU de Bordeaux

• PRS Account: University Hospital, Bordeaux
• Verification Date: January 2022