Protocolized Weaning of High-Flow Nasal Cannula in Adult Patients (PRO-WEAN HFNC)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Hypoxemic Respiratory Failure; High-Flow Nasal Cannula Therapy
• Intervention / Treatment: Behavioral: Usual Care HFNC Weaning; Behavioral: Protocolized HFNC Weaning Strategy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: JIE LI, PhD; Phone Number: 13125634643; Email: jie_li@rush.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Usual Care HFNC Weaning; During this phase, high-flow nasal cannula (HFNC) weaning and discontinuation are performed according to local standard practice without a mandated protocol. Decisions regarding reduction of flow and fraction of inspired oxygen (FiO₂), transition to conventional oxygen therapy, and re-escalation of support are made at the discretion of the treating clinical team.	Behavioral: Usual Care HFNC Weaning; 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.
Experimental: Protocolized HFNC Weaning; Participants receive a standardized HFNC weaning protocol consisting of structured, stepwise reduction of flow and FiO₂ with predefined criteria for discontinuation and 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 design.	Behavioral: Protocolized HFNC Weaning Strategy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients successfully weaned from HFNC on day 5 of 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.	Up to 5 days after study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants successfully weaned from HFNC by Day 1	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.	Up to 1 day after study enrollment
Proportion of participants successfully weaned from HFNC by Day 2	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.	Up to 2 days after study enrollment
Proportion of participants successfully weaned from HFNC by Day 3	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.	Up to 3 days after study enrollment
Proportion of participants successfully weaned from HFNC by Day 4	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.	Up to 4 days after study enrollment
Proportion of participants successfully weaned from HFNC by Day 7	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.	Up to 7 days after study enrollment
HFNC duration (hours)	Total duration of high-flow nasal cannula (HFNC) therapy measured in hours from initiation of HFNC until permanent discontinuation of HFNC during the hospitalization.	From HFNC initiation until hospital discharge, up to 28 days
Oxygen-free days through Day 28	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.	Up to 28 days after study enrollment
HFNC Weaning Duration	Duration in hours from study enrollment to permanent discontinuation of high-flow nasal cannula therapy among participants who meet criteria for weaning success.	From study enrollment until HFNC discontinuation, up to 28 days
Proportion of participants requiring noninvasive ventilation 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.	Within 48 hours after HFNC discontinuation
Proportion of participants requiring re-initiation of HFNC within 48 hours after discontinuation	Proportion of participants who require re-initiation of high-flow nasal cannula therapy within 48 hours after initial discontinuation.	Within 48 hours after HFNC discontinuation
Proportion of participants requiring invasive mechanical ventilation within 48 hours after HFNC discontinuation	Proportion of participants who require endotracheal intubation and invasive mechanical ventilation within 48 hours after HFNC discontinuation.	Within 48 hours after HFNC discontinuation
Duration of invasive mechanical ventilation (hours)	Total duration of invasive mechanical ventilation measured in hours from initiation of endotracheal intubation until successful extubation during hospitalization.	During hospitalization, up to 28 days after enrollment
ICU Length of Stay	Number of days from ICU admission to ICU discharge during the index hospitalization	During index hospitalization, up to 28 days after enrollment
Hospital length of stay (days)	Number of days from hospital admission to hospital discharge during the index hospitalization.	During index hospitalization, up to 28 days after enrollment
ICU mortality	Proportion of participants who die during the ICU stay.	During ICU stay, up to 28 days after enrollment
Hospital mortality	Proportion of participants who die during the index hospitalization.	During hospitalization, up to 28 days after enrollment
Adverse events related to HFNC therapy	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.	During hospitalization, up to 28 days after enrollment

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: Changhai Hospital; Shanghai Zhongshan Hospital; Sir Run Run Shaw Hospital; First Hospital of China Medical University; First Affiliated Hospital of Chongqing Medical University; The First Affiliated Hospital of Xiamen University; Binzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): April 28, 2027

Study Registration Dates

• First Submitted: February 28, 2026
• First Submitted That Met QC Criteria: February 28, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Weaning; Acute hypoxemic respiratory failure; High-flow nasal cannula
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: HFNC weaning

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in the publication (including data dictionaries) will be made available to qualified researchers upon reasonable request and with appropriate institutional ethics approval after publication of the primary results. Requests must include a methodologically sound research proposal and will require approval by the study investigators and participating institutions. Data will be shared under a data use agreement to ensure participant confidentiality and compliance with institutional and regulatory policies.
• IPD Sharing Time Frame: Data will be available beginning 6 months after publication of the primary results and will remain available for 5 years thereafter.
• IPD Sharing Access Criteria: Access to de-identified individual participant data, data dictionaries, statistical analysis plan, and analytic code will be granted to qualified researchers who submit a methodologically sound research proposal. Requests must receive approval from the study investigators and participating institutions and obtain appropriate institutional ethics approval. Data will be shared under a data use agreement to ensure participant confidentiality and compliance with institutional and regulatory requirements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No