Effect of HFNO Therapy on Respiratory Effort After Extubation (T-REX)

High Flow Nasal Oxygen Therapy Re-evaluated from a Conceptual Point of View: Effect on Respiratory Effort and Lung Aeration After Extubation

Rationale: Despite the lack of clear clinical protocols, High Flow Nasal Oxygen (HFNO) is used as post-extubation respiratory support. Although HFNO seems to reduce the need for re-intubation, scepticism on its use persists as the mechanism of action in post-extubation patients remains undefined. Monitoring weaning from invasive mechanical ventilation while monitoring respiratory effort might help to determine the added value of HFNO surrounding extubation. We hypothesize that HFNO, compared to conventional oxygen therapy (COT), prevents de-recruitment of the lung and reduces respiratory effort, and so provides a physiologic clarification for the reduction in the need for reintubation.

Objective: Determine the physiological effect of HFNO compared to COT in the extubation phase regarding respiratory effort and lung aeration.

Study design: A physiologic, randomized clinical study comparing two standard of clinical care therapies.

Study population: Adult patients on invasive mechanical ventilation (IMV) for >72 hours, who are scheduled for extubation.

Intervention (if applicable): Before extubation, patients are randomized to receive COT (reference group) or HFNO as oxygenation regimen after extubation.

Main study parameters/endpoints: The main outcome is the difference in change in lung respiratory muscle effort (mean ΔPES) at 24 hours post-extubation between the study groups. Secondary parameters are differences in changes in respiratory effort at 2 and 4 hours post-extubation, difference in change in lung aeration (mean ΔEELI), differences in tidal volume, dyspnea score, and respiratory and sputum parameters between patients undergoing different post-extubation oxygenation regimens.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure; Post Extubation Acute Respiratory Failure Requiring Reintubation
• Intervention / Treatment: Other: High Flow Nasal Oxygen; Other: Conventional Oxygen Therapy

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstad Ziekenhuis
  • Rotterdam, Netherlands, 3015GD
    • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥ 18 years
• Receiving IMV > 48 hours for any cause
• Successfully completing spontaneous breathing trial (SBT) as per local clinical guideline
• Provided written informed consent, through legal representatives on indication

Exclusion Criteria:

• Any clinical situation preventing appropriate execution of study procedures
• The presence of a tracheostomy
• Any feature that precludes HFNO-initiation
• Indication for NIV such as hypercapnia at end of SBT, or Obstructive/central Sleep Apnoea Syndrome or Obesity Hypoventilation Syndrome with CPAP use in medical history
• Contra-indication for nasogastric tube or inability to perform adequate PES measurements.
• Known diaphragm paralysis defined as elevated hemi-diaphragm on X-ray and evidence of paralysis during ultrasound (i.e. paradoxal diaphragm movement during sniffing)
• Known pregnancy or current breast-feeding

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 Oxygen; 60L/minute. FiO2 according to clinical protocol. Temperature highest tolerated by patient, starting with 37 degrees Celcius.	Other: High Flow Nasal Oxygen; Flow 60L/minute. FiO2 according to clinical protocol. Temperature highest tolerated by patient, starting with 37 degrees Celsius.; Other Names: High Flow Nasal Cannula; Nasal High Flow Therapy
Active Comparator: Conventional Oxygen therapy	Other: Conventional Oxygen Therapy; Nasal Cannula, Venturi Mask or Non-rebreathing mask, according to local clinical protocols

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
delta Esophageal Pressure (ΔPES)	The difference between groups in change in ΔPES in patients 24 hours post-extubation.	At 24 hours after extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
delta global End-expiratory lung impedance (∆EELIglobal)	Difference between the groups in change in mean ∆EELIglobal	At 2, 4 and 24 hours after extubation
Pressure-time product of Esophageal Pressure (PTPES)	The difference between the groups in mean pressure-time product (PTPES) compared to baseline.	At 2,4 and 24 hours after extubation
EIT parameters	∆VARt, ∆EELIdependent, ∆EELInon-dependent compared to baseline (impedance on IMV).	At 2, 4 and 24 hours after extubation
Global Inhomogeneity index		At 2, 4 and 24 hours after extubation
ΔPES	The difference between groups in change in ΔPES after extubation	At 2 and 4 hours post-extubation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyspnea score	Difference in dyspnea sensation between the groups, measured with Visual Analog Scale (VAS, ranging from 0 = No dyspnea until 10 = maximum dyspnea).	At 2 and 24 hours after extubation
Sputum	Difference in sputum aspect and sputum clearance between the study groups, assessed with a 5-point likert scale.	At 2 and 24 hours after extubation
non-invasive positive pressure ventilation (NIPPV)	Treatment escalation	Within 7 days post-extubation
Continuous positive airway pressure (CPAP)	Treatment escalation	Within 7 days post-extubation
invasive mechanical ventilation (IMV).	Treatment escalation	Within 7 days post-extubation
Survival rate	Survival rates	Within 7 days post-extubation

Collaborators and Investigators

• Sponsor: Henrik Endeman
• Collaborators: Franciscus Gasthuis; Maasstad Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): October 22, 2024
• Study Completion (Actual): October 22, 2024

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Extubation; Reintubation; High-flow oxygen; Respiratory Effort; Aeration
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: NL80844.078.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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