Acute Hypoxemic Respiratory Failure, High-Flow Nasal Cannula Therapy
Conditions
Keywords
High-flow nasal cannula, Acute hypoxemic respiratory failure, Weaning
Brief summary
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.
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.
Interventions
BEHAVIORALProtocolized 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.
BEHAVIORALUsual 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.
Sponsors
Rush University Medical Center
The First Affiliated Hospital of Xiamen University
First Hospital of China Medical University
Shanghai Zhongshan Hospital
Binzhou Medical University
First Affiliated Hospital of Chongqing Medical University
Changhai Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a multicenter stepped-wedge cluster randomized trial. Eight hospital clusters will begin in the control phase (usual care) and sequentially transition to the intervention phase (protocolized HFNC weaning) according to a predefined rollout schedule. At each time period, one additional hospital will cross over from control to intervention until all clusters have implemented the protocol. All eligible patients within a cluster will receive the treatment condition assigned to that cluster during each time period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients successfully weaned from HFNC on day 5 of study enrollment | 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants successfully weaned from HFNC by Day 1 | 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. |
| Proportion of participants successfully weaned from HFNC by Day 2 | 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. |
| Proportion of participants successfully weaned from HFNC by Day 3 | 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. |
| Proportion of participants successfully weaned from HFNC by Day 4 | 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. |
| Proportion of participants successfully weaned from HFNC by Day 7 | 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. |
| HFNC duration (hours) | 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. |
| Oxygen-free days through Day 28 | 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. |
| HFNC Weaning Duration | 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. |
| Proportion of participants requiring noninvasive ventilation within 48 hours after HFNC discontinuation | 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. |
| Proportion of participants requiring re-initiation of HFNC within 48 hours after discontinuation | 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. |
| Proportion of participants requiring invasive mechanical ventilation within 48 hours after HFNC discontinuation | Within 48 hours after HFNC discontinuation | Proportion of participants who require endotracheal intubation and invasive mechanical ventilation within 48 hours after HFNC discontinuation. |
| Duration of invasive mechanical ventilation (hours) | 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. |
| ICU Length of Stay | During index hospitalization, up to 28 days after enrollment | Number of days from ICU admission to ICU discharge during the index hospitalization |
| Hospital length of stay (days) | During index hospitalization, up to 28 days after enrollment | Number of days from hospital admission to hospital discharge during the index hospitalization. |
| ICU mortality | During ICU stay, up to 28 days after enrollment | Proportion of participants who die during the ICU stay. |
| Hospital mortality | During hospitalization, up to 28 days after enrollment | Proportion of participants who die during the index hospitalization. |
| Adverse events related to HFNC therapy | 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. |
Countries
United States
Contacts
CONTACTJie Li, PhD
Outcome results
None listed