WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department (WINDSURFER)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome (ARDS); Acute Hypoxic Respiratory Failure
• Intervention / Treatment: Device: Non-Invasive Positive Pressure Ventilation; Device: High Flow Nasal Oxygen

Detailed Description

Acute hypoxemic respiratory failure (AHRF) is a serious medical emergency that frequently presents in the emergency department (ED) and requires immediate respiratory support to prevent further clinical deterioration. Patients with AHRF are at high risk for progression to invasive mechanical ventilation and death, and early management decisions may substantially influence outcomes.

Non-invasive respiratory support (NIRS) is widely used as first-line therapy for AHRF. Two commonly used NIRS strategies are non-invasive positive-pressure ventilation (NIPPV) and high-flow nasal oxygen (HFNO). Both modalities are accepted standards of care; however, their relative effectiveness and safety when applied early in the ED remain uncertain. Prior comparative studies have largely been conducted in intensive care settings, enrolled selected patient populations, or focused on single outcomes such as intubation or mortality. Consequently, equipoise persists regarding the optimal initial NIRS strategy for ED patients with undifferentiated AHRF.

The WINDSURFER trial (WIN ratio analysis to Determine a strategy of non-invasive SUpport for Respiratory Failure in the EmeRgency Department) is designed to compare two strategies of non-invasive respiratory support-NIPPV and HFNO-with respect to clinically meaningful outcomes in adult ED patients with acute hypoxemic respiratory failure.

The trial is conducted at multiple hospitals participating in the NIH funded Strategies to Innovate Emergency Care Clinical Trials Network (SIREN), enabling enrollment across diverse emergency care environments.

The study enrolls adult patients early in their ED course, reflecting the population in which initial respiratory support decisions are most consequential.

Participants are randomly assigned in equal proportions to one of the two study strategies, with allocation managed centrally through a secure electronic system to ensure balance across sites.

The assigned strategy is implemented as the initial approach to non invasive respiratory support for a defined protocolized period, after which ongoing respiratory management is determined by the treating clinical team according to standard clinical practice.

Clinical data are collected from the medical record and study specific assessments to characterize baseline features, treatment course, and in hospital events. Follow up extends through hospitalization and a defined post randomization observation period to ensure complete capture of relevant clinical outcomes.

Ethical Considerations: Because AHRF is a life-threatening emergency requiring immediate intervention and patients frequently lack decision making capacity at presentation, the study is conducted under Exception From Informed Consent (EFIC) in accordance with Food and Drug Administration (FDA) regulations (21 CFR 50.24). Community consultation and public disclosure are completed prior to enrollment at each site. Participants or their Legally Authorized Representatives are informed of enrollment at the earliest feasible opportunity and may withdraw from the study at any time.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Henry E Wang, MD, MS; Phone Number: 614-648-1372; Email: Henry.wang@osumc.edu
• Study Contact Backup: Name: Valerie L Durkalski-Mauldin, PhD; Phone Number: 843-876-1911; Email: durkalsv@musc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • OSU Wexner Medical Center
      • Contact: Michael Hill; Phone Number: 614-293-6185; Email: michael.hill@osumc.edu
      • Principal Investigator: Jason Bischof, MD
      • Contact: Jason Bischof, MD; Phone Number: 614-293-8305; Email: jason.bischof@osumc.edu
    • Columbus, Ohio, United States, 43203
      • Ohio State East Hospital
      • Contact: Michael Hill; Phone Number: 614-293-6185; Email: michael.hill@osumc.edu
      • Principal Investigator: Jason Bischof, MD
      • Contact: Jason Bischof, MD; Phone Number: 614-293-8305; Email: jason.bischof@osumc.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Previous enrollment in WINDSURFER
• A patient-specific contraindication makes one assigned study intervention unsafe

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: Non-Invasive Positive Pressure Ventilation (NIPPV); 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; Oxygen is delivered with positive pressure through a face mask covering the nose and mouth.; Other Names: NIPPV
Active Comparator: High Flow Nasal Oxygen (HFNO); 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; Humidified oxygen is delivered to the participant through a specially-designed nasal cannula.; Other Names: HFNO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects with Major Adverse Pulmonary Event (MAPE)	Composite of: Hospital Death; Ventilator Days; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects with New or worsening pneumonia/pneumonitis	Development or worsening of air-space disease, as identified by radiologist interpretation of chest x-rays and comparison with first chest x-ray.	Up to hospital discharge or 7 days of randomization, whichever comes first.
Number of Subjects with Acute Respiratory Distress Syndrome (ARDS)	Development or worsening of ARDS. Berlin and European Society of Intensive Care Medicine ARDS criteria, both intubated and non-intubated patients: Bilateral opacities on chest x-ray or computed tomography.; Decreased PaO2:FiO2 or SpO2:FiO2 ratio; Respiratory failure not explained by heart failure or volume overload.	Up to hospital discharge or 7 days of randomization, whichever comes first.
Number of Subjects with New or worsening shock	Requirement for vasopressors (>0.2 mcg/kg/min norepinephrine or equivalent) for >1 hour to maintain systolic blood pressure ≥90 mm Hg.	Up to hospital discharge or 72 hours of randomization, whichever comes first.

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Medical University of South Carolina; National Heart, Lung, and Blood Institute (NHLBI); University of Michigan; University of Arizona; Baystate Medical Center
• Investigators: Principal Investigator: 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: Lai Wei, PhD, Ohio State University; Study Director: 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; Principal Investigator: Valerie Durkalski-Mauldin, PhD, Medical University of South Carolina - SIREN Data Coordinating Center

Publications and helpful links

Helpful Links

• WINDSURFER-SIREN Network

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: April 23, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Continuous Positive Airway Pressure; COPD; VAS; Mechanical Ventilation; Chronic Obstructive Pulmonary Disease; Acute Respiratory Distress Syndrome; Invasive Mechanical Ventilation; RR; Renal Replacement Therapy; BiPAP; Respiratory Rate; Visual Analog Scale; Acute Decompensated Heart Failure; NIRS; SpO2; Acute Hypoxemic Respiratory Failure; RRT; NIPPV; PaO2; FiO2; HFNO; PaCO2; Ventilator-Free Days; VFD; Non-Invasive Positive Pressure Ventilation; BPAP; High-Flow Nasal Oxygen; Expiratory Positive Airway Pressure; P-SILI; WR; MV; IMV; EPAP; Inspired Oxygen Fraction; IPAP; Inspiratory Positive Airway Pressure; MAPE; Major Adverse Pulmonary Events; Non-Invasive Respiratory Support; Partial pressure of carbon dioxide in arterial blood; Partial pressure of oxygen in arterial blood; P:F; Ratio of PaO2 to FiO2; Patient Self-Inflicted Lung Injury; RSFD; Respiratory Support Free Days; S:F; Ratio of SpO2 to FiO2; Transcutaneous measurement of peripheral arterial saturation; UADE; Unanticipated Adverse Device Effects; VDays; Ventilator Days; WINDSURFER; WIN ratio analysis to determine a strategy of non-invasive support for respiratory failure in the emergency department trial; WIN Ratio; Bilevel Positive Airway Pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Insufficiency
• Other Study ID Numbers: UG3HL175260 (U.S. NIH Grant/Contract); U24HL175258 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: After data set locked and submitted to BioLINCC.
• IPD Sharing Access Criteria: Request to BioLINCC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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