NCT07558265

Brief Summary

The purpose of this clinical trial is to determine the best initial non-invasive respiratory support (NIRS) strategy for adults who present to the emergency department with acute hypoxemic respiratory failure, a condition in which blood oxygen levels are dangerously low and require urgent treatment. This study compares two commonly used non-invasive respiratory support strategies to evaluate their effectiveness and safety, based on important patient outcomes during hospitalization, including survival, the need for invasive mechanical ventilation, and the duration of respiratory support. Participants will be randomly assigned (with an equal chance) to receive one of the following treatments:

  • Non-Invasive Positive Pressure Ventilation (NIPPV): Oxygen delivered under pressure through a face mask.
  • High-Flow Nasal Oxygen (HFNO): Oxygen delivered at high-flow through a specially designed nasal cannula placed in the nostrils. Researchers will compare the two treatment strategies using a hierarchical assessment of major pulmonary outcomes, including:
  • Hospital survival
  • Days on mechanical ventilation
  • Duration of non-invasive respiratory support As part of the study, researchers will collect:
  • Blood and urine samples
  • Physiologic measurements (such as chest movement measured through sensors placed on the skin)
  • Information from participants' medical records

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
500

participants targeted

Target at P75+ for not_applicable

Timeline
62mo left

Started Jul 2026

Longer than P75 for not_applicable

Geographic Reach
1 country

19 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 23, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 30, 2026

Completed
2 months until next milestone

Study Start

First participant enrolled

July 1, 2026

Expected
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2031

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2031

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

5.1 years

First QC Date

April 23, 2026

Last Update Submit

April 30, 2026

Conditions

Keywords

Acute Hypoxemic Respiratory FailureAcute Decompensated Heart FailureAcute Respiratory Distress SyndromeBiPAPBPAPCOPDChronic Obstructive Pulmonary DiseaseContinuous Positive Airway PressureHFNOHigh-Flow Nasal OxygenEPAPExpiratory Positive Airway PressureFiO2Inspired Oxygen FractionIMVInvasive Mechanical VentilationIPAPInspiratory Positive Airway PressureMAPEMajor Adverse Pulmonary EventsMVMechanical VentilationNIRSNon-Invasive Respiratory SupportNIPPVNon-Invasive Positive Pressure VentilationPaCO2Partial pressure of carbon dioxide in arterial bloodPaO2Partial pressure of oxygen in arterial bloodP:FRatio of PaO2 to FiO2RRRespiratory RateP-SILIPatient Self-Inflicted Lung InjuryRRTRenal Replacement TherapyRSFDRespiratory Support Free DaysS:FRatio of SpO2 to FiO2SpO2Transcutaneous measurement of peripheral arterial saturationUADEUnanticipated Adverse Device EffectsVASVisual Analog ScaleVDaysVentilator DaysVFDVentilator-Free DaysWINDSURFERWIN ratio analysis to determine a strategy of non-invasive support for respiratory failure in the emergency department trialWRWIN RatioBilevel Positive Airway Pressure

Outcome Measures

Primary Outcomes (1)

  • Number of Subjects with Major Adverse Pulmonary Event (MAPE)

    Composite of: 1. Hospital Death 2. Ventilator Days 3. Non-Invasive Respiratory Support (NIRS) Hours

    a) Hospital Death up to 28 days after randomization b) Maximum of 28 ventilator days c) Maximum of 24 NIRS hours

Secondary Outcomes (3)

  • Number of Subjects with New or worsening pneumonia/pneumonitis

    Up to hospital discharge or 7 days of randomization, whichever comes first.

  • Number of Subjects with Acute Respiratory Distress Syndrome (ARDS)

    Up to hospital discharge or 7 days of randomization, whichever comes first.

  • Number of Subjects with New or worsening shock

    Up to hospital discharge or 72 hours of randomization, whichever comes first.

Study Arms (2)

Non-Invasive Positive Pressure Ventilation (NIPPV)

ACTIVE COMPARATOR

Participants (randomized) who are experiencing acute hypoxemic respiratory failure will be placed on Non-Invasive Positive Pressure Ventilation (NIPPV), by face mask.

Device: Non-Invasive Positive Pressure Ventilation

High Flow Nasal Oxygen (HFNO)

ACTIVE COMPARATOR

Participants (randomized) who are experiencing acute hypoxemic respiratory failure will be placed on humidified High-Flow Nasal Oxygen (HFNO), delivered to the participant through a specially designed nasal cannula.

Device: High Flow Nasal Oxygen

Interventions

Oxygen is delivered with positive pressure through a face mask covering the nose and mouth.

Also known as: NIPPV
Non-Invasive Positive Pressure Ventilation (NIPPV)

Humidified oxygen is delivered to the participant through a specially-designed nasal cannula.

Also known as: HFNO
High Flow Nasal Oxygen (HFNO)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • Presenting to the Emergency Department (ED) with Acute Hypoxemic Respiratory failure (AHRF), defined as:
  • \[(respiratory rate ≥25 breaths/min) AND (requiring ≥6 L/min of oxygen required to maintain SpO2 ≥90%), OR SpO2:FiO2 ratio\<250\] OR
  • Arrival at ED on prehospital Non-Invasive Respiratory Support (NIRS).
  • Clinical need for NIRS
  • Randomization ≤2 hours after identification of need for NIRS
  • Randomization ≤6 hours of ED arrival

You may not qualify if:

  • Urgent need for intubation
  • Cardiac arrest
  • Respiratory arrest
  • Patient not located in the ED
  • Craniofacial anatomic features that prohibit either Non-Invasive Positive Pressure Ventilation (NIPPV) or High Flow Nasal Oxygen (HFNO) interface
  • Tracheostomy or laryngectomy stoma
  • Hemodynamic instability requiring \>0.2mcg/kg/min of norepinepherine (or equivalent) to maintain mean arterial pressure \>65mmHg
  • Pre-existing "do not resuscitate" or "do not intubate" order
  • Home use of non-invasive positive-pressure ventilation for respiratory support of a medical condition other than sleep apnea
  • Transferred from another Emergency Department
  • History of advanced chronic obstructive pulmonary disease
  • History of advanced heart failure
  • Presence of opt-out identification
  • Prisoner
  • Known or apparent pregnant
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Banner University Medical Center Tucson

Tucson, Arizona, 85719, United States

Location

UCSD La Jolla

San Diego, California, 92037, United States

Location

UCSD Hillcrest

San Diego, California, 92103, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60615, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01107, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48207, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55423, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State East Hospital

Columbus, Ohio, 43203, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Links

MeSH Terms

Conditions

Respiratory Distress SyndromeRespiratory InsufficiencyPulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration DisordersLung Diseases, ObstructiveChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Henry E Wang, MD, MS

    Ohio State University

    PRINCIPAL INVESTIGATOR
  • Jarrod Mosier, MD

    University of Arizona

    PRINCIPAL INVESTIGATOR
  • Mark Tidswell, MD

    Baystate Health

    PRINCIPAL INVESTIGATOR
  • William Meurer, MD

    University of Michigan - Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) Clinical Coordinating Center

    STUDY DIRECTOR
  • Robert Silbergleit, MD

    University of Michigan - SIREN Clinical Coordinating Center

    STUDY DIRECTOR
  • Valerie Durkalski-Mauldin, PhD

    Medical University of South Carolina - SIREN Data Coordinating Center

    PRINCIPAL INVESTIGATOR
  • Lai Wei, PhD

    Ohio State University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Henry E Wang, MD, MS

CONTACT

Valerie L Durkalski-Mauldin, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Non-Invasive Positive Pressure Ventilation (NIPPV) or High Flow Nasal Oxygen (HFNO), maintained for 24 hours from randomization. NIPPV will consist of Bilevel Positive Airway Pressure (BPAP).
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 23, 2026

First Posted

April 30, 2026

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

August 1, 2031

Study Completion (Estimated)

August 1, 2031

Last Updated

May 5, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

After participant enrollment and follow up have been completed and the database has been locked, the Data Coordinating Center (DCC) will prepare a de-identified dataset that will be submitted to the NHLBI data repository managed by the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) or else where as arranged with the Institute. Requests to access the shared data after the trial is completed will be handled by the BioLINCC Coordinating Center.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
After data set locked and submitted to BioLINCC.
Access Criteria
Request to BioLINCC.

Locations