Predicting High-Flow Nasal Oxygen Failure at 30 Minutes Using a Physiology-Informed Dual-Domain Model

NCT07366541 | Completed DMC

• 1 other identifier: [2025]232 and [2025] 30
• Study Type: observational
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-center, two-stage translational study develops and validates a physiology-informed dual-domain model for ultra-early (30-minute) prediction of high-flow nasal oxygen (HFNO) failure in patients with acute hypoxemic respiratory failure. The study includes a physiological validation cohort (n=24) to anchor the EIT-derived Flow Index (EFI) as a marker of inspiratory effort, followed by a temporally separated clinical derivation cohort (n=57) and independent validation cohort (n=58). Candidate predictors are screened from 1,328 clinical features. The final dual-domain model integrates persistent physiological burden (baseline PaCO₂ and 30-minute EFI) with short-term dynamic adaptation (ΔRR and ΔSpO₂ over 30 minutes). The model's discrimination is tested prospectively without refitting.

Conditions

Electrical Impedance Tomography (EIT); Acute Respiratory Failure; High-Flow Nasal Oxygen Therapy

Outcome Measures

Primary Outcomes (1)

• HFNC Failure Rate(Early Reassessment at 30 Minutes)

  HFNO failure was defined as escalation to noninvasive ventilation (NIV) or endotracheal intubation due to refractory hypoxemia, progressive respiratory acidosis, severe respiratory distress, or hemodynamic instability. Within-tier adjustments (increasing flow or FiO₂ without changing support modality) were NOT considered failure.

  within 30 minutes after HFNO initiation (with monitoring of outcomes up to hospital discharge)

Secondary Outcomes (3)

• Physiological Validation of EFI

  During physiological measurements in mechanically ventilated patients (performed before the clinical HFNO cohort; within 48 hours of ICU admission)

• Persistent Abnormality at 30 Minutes

  within 30 minutes after HFNO initiation

• Divergent Short-Term Response Trajectories

  Baseline to 30 minutes after HFNO initiation

Study Arms (5)

Physiological Validation Cohort

Mechanically ventilated patients with acute respiratory distress syndrome (ARDS) receiving pressure support ventilation. Intervention: Simultaneous electrical impedance tomography (EIT) and esophageal pressure monitoring at three sequential pressure support levels (PSmin, PSbase, PSmax). Outcome measures: EIT-derived Flow Index (EFI), esophageal pressure swing (ΔPes), pressure-time product per minute (PTP/min). No HFNO administered.

Device: Mechanical Ventilation Support; Device: Electrical Impedance Tomography Monitoring

Derivation Cohort - HFNO Success

High-risk patients with acute hypoxemic respiratory failure (AHRF) initiated on high-flow nasal oxygen (HFNO) who achieved clinical stabilization without requiring escalation to noninvasive ventilation or endotracheal intubation within 72 hours. Intervention: EIT monitoring and bedside data collection (heart rate, respiratory rate, arterial blood gases, SpO₂, ROX index, EMOX index) at baseline (HFNO initiation) and at 30 minutes. No additional device intervention.

Other: High-Flow Nasal Oxygen Therapy; Device: High-Flow Nasal Oxygen Therapy With EIT Monitoring

Derivation Cohort - HFNO Failure

High-risk patients with AHRF initiated on HFNO who required escalation to noninvasive ventilation or endotracheal intubation within 72 hours due to refractory hypoxemia, progressive respiratory acidosis, severe respiratory distress, or hemodynamic instability. Intervention: EIT monitoring and bedside data collection (same variables as success group) at baseline and 30 minutes. Escalation decision guided by predefined objective criteria, not by EIT data.

Other: High-Flow Nasal Oxygen Therapy; Device: High-Flow Nasal Oxygen Therapy With EIT Monitoring

Validation Cohort - HFNO Success

Independent temporally separate cohort of high-risk AHRF patients initiated on HFNO who achieved clinical stabilization without escalation. Same inclusion/exclusion criteria as derivation cohort. Intervention: Identical 30-minute reassessment protocol: EIT monitoring and bedside data collection at baseline and 30 minutes. Model tested prospectively without coefficient refitting.

Device: High-Flow Nasal Oxygen Therapy With EIT Monitoring

Validation Cohort - HFNO Failure

Independent temporally separate cohort of high-risk AHRF patients initiated on HFNO who required escalation to noninvasive ventilation or endotracheal intubation. Same escalation criteria as derivation cohort. Intervention: EIT monitoring and bedside data collection at baseline and 30 minutes. The fixed dual-domain model (baseline PaCO₂, 30-min EFI, ΔRR, ΔSpO₂) derived from the derivation cohort was applied without refitting to assess discrimination.

Device: High-Flow Nasal Oxygen Therapy With EIT Monitoring

Interventions

Mechanical Ventilation Support DEVICE

Patients received pressure support ventilation at three sequentially adjusted levels (PSmin, PSbase, PSmax). Breathing parameters were continuously monitored using an electrical impedance tomography (EIT) device, and inspiratory effort was invasively measured via an esophageal pressure catheter.

Physiological Validation Cohort

Electrical Impedance Tomography Monitoring DEVICE

PulmoVista 500 EIT device (Dräger Medical, Lübeck, Germany) was used for continuous real-time monitoring of regional lung ventilation.

Physiological Validation Cohort

High-Flow Nasal Oxygen Therapy OTHER

Patients received HFNO as part of standard clinical care for acute hypoxemic respiratory failure. The treatment was titrated by the clinical team based on physiological parameters (SpO₂, RR, ABG), aiming to maintain SpO₂ ≥ 92% and reduce signs of respiratory distress.

Derivation Cohort - HFNO Failure; Derivation Cohort - HFNO Success

High-Flow Nasal Oxygen Therapy With EIT Monitoring DEVICE

Patients received standard-of-care HFNO for AHRF. Additionally, a PulmoVista 500 EIT device was used to monitor lung ventilation and derive the EFI at baseline and 30 minutes.

Derivation Cohort - HFNO Failure; Derivation Cohort - HFNO Success; Validation Cohort - HFNO Failure; Validation Cohort - HFNO Success

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with acute respiratory failure receiving HFNO

You may qualify if:

• Age ≥18 years
• Acute hypoxemic respiratory failure (AHRF) requiring HFNO initiation
• At least one of the following high-risk criteria: a) PaO₂/FiO₂ ≤200 mmHg or FiO₂ ≥0.40 to maintain SpO₂ ≥92%; b) Respiratory rate ≥25/min; c) APACHE II score ≥12; d) Bilateral infiltrates on chest imaging

You may not qualify if:

• Neuromuscular disease affecting spontaneous breathing
• Pregnancy
• Contraindication to EIT (e.g., chest wall wounds, pacemaker)
• Do-not-intubate order
• Hypercapnic respiratory failure as primary diagnosis (PaCO₂ \>50 mmHg with pH \<7.30 at baseline, unless mixed mechanism)

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Department of Critical Care Medicine，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Study Officials

• Hongping Qu

  Department of Critical Care Medicine，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: January 26, 2026
• Study Start: May 1, 2025
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: June 17, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)