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

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.

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