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NCT Number: NCT07452406

Protocolized Weaning of High-Flow Nasal Cannula in Adult Patients

High-flow nasal cannula (HFNC) is a type of oxygen therapy commonly used in adults with breathing problems. While HFNC can help patients avoid breathing tubes and improve oxygen levels, there is no standard method for deciding how and when to reduce and stop this therapy once a patient improves. In many hospitals, these decisions vary from clinician to clinician.

This study will compare usual care with a standardized step-by-step plan for reducing HFNC support. Eight hospitals will participate and will switch from usual care to the standardized plan at different time points during the study.

The main goal is to determine whether the standardized weaning plan increases the number of patients who can successfully stop HFNC within 5 days. The study will also evaluate how long patients remain on HFNC, whether they need additional breathing support, and how long they stay in the hospital.

The results may help develop clearer guidance for safely and efficiently stopping HFNC therapy.

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Key information

Conditions

Acute Hypoxemic Respiratory Failure High-Flow Nasal Cannula Therapy Respiration Disorders Respiratory Insufficiency Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Rush University Medical Center

Chicago, Illinois, 60612, United States

About this study

High-flow nasal cannula (HFNC) therapy has become a standard treatment for acute hypoxemic respiratory failure. Although evidence supports its use for improving oxygenation and reducing intubation risk, guidance on how to discontinue HFNC remains limited. Current weaning practices are highly variable across institutions and clinicians. This variability may contribute to either premature discontinuation, leading to respiratory deterioration, or prolonged therapy, which may delay ICU discharge and increase healthcare utilization.

This trial evaluates implementation of a standardized HFNC weaning protocol across multiple hospitals using a stepped-wedge cluster randomized design. The intervention focuses on structured, progressive reduction of HFNC flow and fraction of inspired oxygen (FiO₂), with predefined criteria for discontinuation and re-escalation of support.

The stepped-wedge approach allows sequential implementation of the protocol across participating hospitals while accounting for secular trends and inter-site practice variability. The study is designed to determine whether protocolized weaning improves efficiency and clinical outcomes compared with usual care.

Findings from this trial are intended to inform evidence-based guidance for HFNC liberation strategies in adult patients with acute hypoxemic respiratory failure.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patients ≥ 18 years
  • Receiving HFNC for ≥12 hours
  • Receiving HFNC to treat acute hypoxemic respiratory failure, defined as requirement of FIO2 ≥ 0.5 to maintain SpO2 at 90-97% and Evidence of increased work of breathing at initiation (e.g., tachypnea with respiratory rate > 20-25/min, or accessory muscle use), including:
  • Patients using HFNC to avoid intubation
  • Post-extubated patients who develop acute hypoxemic respiratory failure, regardless of respiratory support device prior to HFNC use.
  • The bedside clinical team determines that HFNC weaning is clinically appropriate
  • Demonstrates clinical stability, defined as:
  • Respiratory rate ≤ 25 breaths per minute without use of accessory respiratory muscles
  • SpO₂ > 90% on HFNC
  • HFNC FiO₂ ≤ 0.80

Exclusion criteria

  • • Planned procedures requiring intubation
  • Hypercapnia (PaCO2 ≥ 45 mmHg)
  • Receiving extracorporeal membrane oxygenation (ECMO)
  • Receiving continuous aerosol therapy via HFNC (e.g., inhaled nitric oxide [iNO], epoprostenol, or continuous albuterol)
  • Receiving chronic home use of HFNC, CPAP, or noninvasive ventilation therapy to treat chronic respiratory failure
  • Receiving HFNC as preventative post-extubation therapy, defined as HFNC use immediately after extubation for less than 48 hr in the absence of clinical signs of respiratory failure.

Treatment and study plan

Protocolized HFNC Weaning Strategy

Behavioral

A standardized high-flow nasal cannula (HFNC) weaning protocol consisting of structured, stepwise reduction of flow and fraction of inspired oxygen (FiO₂) with predefined criteria for discontinuation and predefined criteria for treatment failure requiring re-escalation of respiratory support. The protocol is implemented at the hospital level during the intervention phase of the stepped-wedge cluster randomized design.

Usual Care HFNC Weaning

Behavioral

High-flow nasal cannula (HFNC) weaning and discontinuation are performed according to local standard clinical practice without a mandated protocol. Decisions regarding reduction of flow and fraction of inspired oxygen (FiO₂), transition to conventional oxygen therapy, and escalation of respiratory support are made at the discretion of the treating clinical team.

Primary outcomes

  1. Proportion of patients successfully weaned from HFNC on day 5 of study enrollment

    Time frame: Up to 5 days after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and breathing on conventional oxygen therapy or room air without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation. Participants remaining on HFNC beyond Day 5 are considered weaning failures.

Secondary outcomes

  1. Proportion of participants successfully weaned from HFNC by Day 1

    Time frame: Up to 1 day after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation.

  2. Proportion of participants successfully weaned from HFNC by Day 2

    Time frame: Up to 2 days after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation.

  3. Proportion of participants successfully weaned from HFNC by Day 3

    Time frame: Up to 3 days after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation.

  4. Proportion of participants successfully weaned from HFNC by Day 4

    Time frame: Up to 4 days after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation.

  5. Proportion of participants successfully weaned from HFNC by Day 7

    Time frame: Up to 7 days after study enrollment

    HFNC weaning success is defined as discontinuation of high-flow nasal cannula therapy with the participant alive and without need for noninvasive ventilation, CPAP, invasive mechanical ventilation, or re-initiation of HFNC within 24 hours of discontinuation.

  6. HFNC duration (hours)

    Time frame: From HFNC initiation until hospital discharge, up to 28 days

    Total duration of high-flow nasal cannula (HFNC) therapy measured in hours from initiation of HFNC until permanent discontinuation of HFNC during the hospitalization.

  7. Oxygen-free days through Day 28

    Time frame: Up to 28 days after study enrollment

    Number of days alive and not receiving any supplemental oxygen (including HFNC, conventional oxygen therapy, noninvasive ventilation, or invasive mechanical ventilation) during the first 28 days after study enrollment. Participants who die before Day 28 will be assigned zero oxygen-free days.

  8. HFNC Weaning Duration

    Time frame: From study enrollment until HFNC discontinuation, up to 28 days

    Duration in hours from study enrollment to permanent discontinuation of high-flow nasal cannula therapy among participants who meet criteria for weaning success.

  9. Proportion of participants requiring noninvasive ventilation within 48 hours after HFNC discontinuation

    Time frame: Within 48 hours after HFNC discontinuation

    Proportion of participants who require initiation of noninvasive ventilation (e.g., BiPAP or CPAP for respiratory failure) within 48 hours after HFNC discontinuation.

  10. Proportion of participants requiring re-initiation of HFNC within 48 hours after discontinuation

    Time frame: Within 48 hours after HFNC discontinuation

    Proportion of participants who require re-initiation of high-flow nasal cannula therapy within 48 hours after initial discontinuation.

  11. Proportion of participants requiring invasive mechanical ventilation within 48 hours after HFNC discontinuation

    Time frame: Within 48 hours after HFNC discontinuation

    Proportion of participants who require endotracheal intubation and invasive mechanical ventilation within 48 hours after HFNC discontinuation.

  12. Duration of invasive mechanical ventilation (hours)

    Time frame: During hospitalization, up to 28 days after enrollment

    Total duration of invasive mechanical ventilation measured in hours from initiation of endotracheal intubation until successful extubation during hospitalization.

  13. ICU Length of Stay

    Time frame: During index hospitalization, up to 28 days after enrollment

    Number of days from ICU admission to ICU discharge during the index hospitalization

  14. Hospital length of stay (days)

    Time frame: During index hospitalization, up to 28 days after enrollment

    Number of days from hospital admission to hospital discharge during the index hospitalization.

  15. ICU mortality

    Time frame: During ICU stay, up to 28 days after enrollment

    Proportion of participants who die during the ICU stay.

  16. Hospital mortality

    Time frame: During hospitalization, up to 28 days after enrollment

    Proportion of participants who die during the index hospitalization.

  17. Adverse events related to HFNC therapy

    Time frame: During hospitalization, up to 28 days after enrollment

    Incidence of adverse events during HFNC therapy, including but not limited to skin breakdown, nasal or facial injury, epistaxis, or other clinically significant complications documented during hospitalization.

Study contacts

Contact information is provided by the study sponsor or research team.

Jie Li, PhD

CONTACT

[email protected]

13125634643

Sponsors and collaborators

Lead sponsor

Rush University Medical Center

Other

Collaborators

  • Binzhou Medical University
  • Changhai Hospital
  • First Affiliated Hospital of Chongqing Medical University
  • First Hospital of China Medical University
  • Shanghai Zhongshan Hospital
  • The First Affiliated Hospital of Xiamen University

Registry information

Official study title

Protocolized Weaning of High-Flow Nasal Cannula in Adult Patients: A Stepped-Wedge Cluster Randomized Trial (PRO-WEAN HFNC)

Acronym: PRO-WEAN HFNC

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Mar 5, 2026
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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