1/2 WIN Ratio Analysis to Determine a Strategy of Non-Invasive SUpport for Respiratory Failure in the EmeRgency Department (WINDSURFER)

About This Grant

PROJECT SUMMARY We propose the WINDSURFER trial to answer one of the signature questions of emergency care; “What is the best non-invasive respiratory support (NIRS) strategy for treating acute hypoxemic respiratory failure (AHRF) in the Emergency Department (ED)?” AHRF is the syndrome of impaired breathing resulting in low blood oxygen levels, most commonly from lung or other infections, acute decompensated heart failure (ADHF) and chronic obstructive pulmonary disease (COPD). AHRF is a major public health problem as evidenced by its seasonal and pandemic surges and the >100,000 associated deaths each year in the United States. Aggressive treatment of AHRF at its earliest stages in the Emergency Department (ED) is essential to prevent progression to death. Non-Invasive Respiratory Support (NIRS) is an important and widely used rescue treatment for AHRF that provides effective high-level breathing support without the pitfalls and consequences of mechanical ventilation. The two forms of NIRS are: 1) Non-Invasive Positive Pressure Ventilation (NIPPV), which includes continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP)], and 2) Heated High-Flow Nasal Oxygen (HFNO). NIPPV supports breathing by delivering high pressured oxygen through a tight-fitting face mask. In contrast, HFNO supports breathing by delivering high flows of heated and humidified oxygen through a specially designed nasal tube. The best NIRS strategy for AHRF is unknown. The optimal treatment for AHRF must be effective, safe, easy to deploy, comfortable for patients and effective across a spectrum of diseases and comorbidities. We propose a new clinical trial, WIN ratio analysis to Determine a strategy of non-invasive SUpport for Respiratory Failure in the EmeRgency Department (WINDSURFER), to determine the best initial NIRS strategy for patients presenting to the ED with AHRF. We will execute the trial using EDs selected from the NIH Strategies to Innovate Emergency Care Clinical Trials Network (SIREN). We will randomize adult ED patients (n=500) with AHRF to a treatment strategy of 12 hours of NIPPV or HFNO. The primary outcome is the hierarchical Major Adverse Pulmonary Events (MAPE): 1) hospital mortality, 2) ventilator-free days, and 3) NIRS hours. We will compare differences in MAPE between NIPPV and HFNO using the Win Ratio, a novel technique to assess differences in a hierarchical composite outcome. Our aims are: Aim I: Determine the effectiveness of ED NIRS strategies (NIPPV vs. HFNO) upon AHRF outcomes. We will test the hypothesis that HFNO is superior to NIPPV, as demonstrated by lower MAPE. Aim II: Evaluate the safety of ED NIRS strategies (NIPPV vs. HFNO) in AHRF. We will evaluate the risk differences between NIPPV and HFNO for the development or worsening of three specific safety outcomes: 1) pneumonia/ pneumonitis, 2) ARDS and 3) shock.