Post-Extubation High-Flow Nasal Cannula Versus Non-Invasive Ventilation in Type II Respiratory Failure

Post-Extubation Support Using Nasal Humidified High-Flow Oxygen Versus Non-Invasive Positive Pressure Mechanical Ventilation in Preventing Reintubation Among Patients With Type II Respiratory Failure

Acute hypercapnic respiratory failure is characterized by elevated arterial carbon dioxide levels and commonly occurs in patients with chronic respiratory diseases. Patients with type II respiratory failure who experience difficult weaning from invasive mechanical ventilation are at increased risk of post-extubation respiratory failure and reintubation. This randomized clinical trial compared high-flow nasal cannula (HFNC) with non-invasive ventilation (NIV) as respiratory support immediately after extubation in patients aged over 50 years with type II respiratory failure and difficult weaning. The primary objective was to compare reintubation rates at 72 hours and 7 days after extubation.

Study Overview

• Status: Completed
• Conditions: Hypercapnic Respiratory Failure; Type II Respiratory Failure
• Intervention / Treatment: Device: High-Flow Nasal Cannula (HFNC); Device: Non-Invasive Ventilation (NIV)

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Qalyubia Governorate
    • Banhā, Qalyubia Governorate, Egypt, 13511
      • Benha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >50 years.
• Type II respiratory failure.
• Receiving invasive mechanical ventilation.
• Difficult weaning from invasive mechanical ventilation, defined as failure to wean after 3-7 days of weaning attempts.
• Fulfillment of predefined clinical criteria for extubation.
• Written informed consent.

Exclusion Criteria:

• Refusal to participate or absence of informed consent.
• Contraindication to NIV, including hemodynamic instability, excessive respiratory secretions with poor expectoration ability, oral or facial trauma, or recent esophageal surgery.
• Poor short-term prognosis, including a very high risk of death within 7 days or receipt of palliative care.
• Severe failure of another organ system, including severe cardiac, neurological, renal, or hepatic failure.
• Existing tracheostomy.
• Loss to follow-up resulting in uncertain 28-day survival.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Flow Nasal Cannula (HFNC) Group; Participants randomized to this group received high-flow nasal cannula immediately after extubation. The initial airflow was set at 50 L/min and subsequently adjusted according to patient tolerance. Absolute humidity was set at 44 mg H2O/L and temperature at 37°C. Therapy was adjusted to maintain SpO2 between 88% and 92% and respiratory rate below 30 breaths/min or at the pre-extubation baseline. Escalation to NIV or invasive mechanical ventilation because of respiratory failure was considered HFNC treatment failure.	Device: High-Flow Nasal Cannula (HFNC); Heated and humidified high-flow oxygen was delivered through a nasal cannula immediately after extubation. The device provided adjustable high-flow oxygen to achieve the predefined oxygenation and respiratory-rate targets.
Active Comparator: Non-Invasive Ventilation (NIV) Group; Participants randomized to this group received non-invasive ventilation immediately after extubation through a conventional oronasal mask using spontaneous/timed (S/T) mode. Expiratory positive airway pressure was initially set at 4 cmH2O and inspiratory pressure at 8 cmH2O, with subsequent adjustment according to patient tolerance and to achieve a tidal volume of 6-8 mL/kg. Pressure support and FiO2 were adjusted to maintain SpO2 between 88% and 92%, respiratory rate ≤30 breaths/min or at the pre-extubation baseline, and PaCO2 between 45 and 60 mmHg or at the most recent pre-extubation value. Requirement for invasive mechanical ventilation was considered NIV treatment failure.	Device: Non-Invasive Ventilation (NIV); Positive-pressure ventilatory support was delivered immediately after extubation through a conventional oronasal mask using spontaneous/timed (S/T) ventilation, with pressure and inspired oxygen adjusted according to predefined respiratory and gas-exchange targets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reintubation Rate	Number and proportion of participants requiring reinstitution of invasive mechanical ventilation after planned extubation.	At 72 hours and 7 days after extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure Rate	Treatment failure was defined as escalation from HFNC to NIV or invasive mechanical ventilation in the HFNC group and requirement for invasive mechanical ventilation in the NIV group.	Within 48 hours after extubation
Ventilator-Free Days at Day 28	Number of days alive and free from invasive mechanical ventilation during the first 28 days after randomization.	During the first 28 days after extubation
Duration of Post-Extubation Respiratory Support	Duration of respiratory support with HFNC or NIV following extubation.	Through 72 hours after extubation
Arterial Blood pH	Arterial blood pH measured by arterial blood gas analysis after extubation.	At 1, 12, 24, and 48 hours after extubation
Arterial Partial Pressure of Carbon Dioxide (PaCO2)	PaCO2 measured by arterial blood gas analysis after extubation.	At 1, 12, 24, and 48 hours after extubation
Arterial Bicarbonate (HCO3)	Arterial bicarbonate concentration measured as part of arterial blood gas analysis after extubation.	At 1, 12, 24, and 48 hours after extubation
PaO2/FiO2 Ratio	Ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2), used to assess oxygenation after extubation.	At 1, 12, 24, and 48 hours after extubation
Post-Extubation Complications	Incidence of post-extubation complications were recorded during follow-up in the HFNC and NIV groups.	From extubation through 28 days after randomization

Collaborators and Investigators

• Sponsor: Benha University
• Investigators: Study Director: Ahmed Mostafa Abdelhamid, Professor of Anesthesia, Benha University; Principal Investigator: Fatma Ahmed Abdelfattah, MD Anesthesia and intensive ca, Benha University; Study Chair: Mohamed Shaker Sadek, MD chest diseases, Benha University

Publications and helpful links

General Publications

• Thille AW, Harrois A, Schortgen F, Brun-Buisson C, Brochard L. Outcomes of extubation failure in medical intensive care unit patients. Crit Care Med. 2011 Dec;39(12):2612-8. doi: 10.1097/CCM.0b013e3182282a5a.
• Comellini V, Pacilli AMG, Nava S. Benefits of non-invasive ventilation in acute hypercapnic respiratory failure. Respirology. 2019 Apr;24(4):308-317. doi: 10.1111/resp.13469. Epub 2019 Jan 12.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Actual): November 15, 2025
• Study Completion (Actual): November 15, 2025

Study Registration Dates

• First Submitted: March 15, 2025
• First Submitted That Met QC Criteria: April 6, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 22, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Non-invasive ventilation; Hypercapnia; Reintubation; High-flow nasal cannula; Post-extubation; Type II respiratory failure; Difficult weaning
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Respiratory Insufficiency; Hypercapnia; Hypoventilation; Therapeutics; Airway Management; Respiratory Therapy; Respiration, Artificial; Noninvasive Ventilation
• Other Study ID Numbers: MD4-2-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Clinical Study Report
   Information identifier: Arnaud W Thille et al
   Information comments: Extubation failure is associated with a poor prognosis, but the respective roles for reintubation per se and underlying disease severity remain unclear. Our objectives were to evaluate the impact of failed extubation, whether planned or unplanned, on patient outcomes and to identify a patient subset at risk for extubation failure.

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