A Phase 4, Multicenter, Cluster Randomized, Open-label, Intervention Versus Usual Care, Controlled Study on the Effect of Emergency Department Initiation of Airsupra on Asthma Outcomes

Acute asthma (or asthma exacerbation) is common and costly. In the USA, acute asthma accounts for approximately 2 million emergency department (ED) visits per year; approximately 10-20% of patients are admitted and, among those discharged, approximately 15-20% relapse (i.e., return to the ED for further treatment of their index exacerbation). A 2000 Cochrane review evaluated if starting inhaled corticosteroids (ICS) at ED discharge would lower risk of relapse during the 2-3 weeks after the ED visit. The meta-analysis included three randomized controlled trials (RCTs) and found borderline significant evidence that ICS initiation lowered risk of relapse during the 2-3 weeks after ED discharge (total n=909 patients; OR 0.68; 95%CI 0.46-1.02).

For decades, asthma experts have tried to increase ED-based prescribing of ICS to ED patients with asthma but uptake has been slow. In addition to reluctance among ED clinicians to prescribe a "lifelong" medication, a challenge has been patients' perception that they do not receive any immediate symptom relief from the new (ICS only) inhaler - i.e., "it does not work as well" as their regular (albuterol) inhaler. FDA approval of Airsupra (with both albuterol and budesonide in one inhaler) provides a unique opportunity to introduce ICS (along with albuterol) to ED patients with acute asthma.

The proposed trial is a cluster randomized, open-label, intervention vs usual care, controlled study on the effect of ED initiation of Airsupra on acute asthma recurrence at 3 months (primary outcome) - i.e., a combination of acute asthma "relapse" (by 3 weeks) plus subsequent exacerbations. The trial is powered to assess a 33% reduction in recurrence at 3 months and will have ample power to explore asthma control, both overall and in important subgroups (e.g., stratified by age, sex, race/ethnicity, BMI, current asthma medications, and number of ED visits for acute asthma in the past year). Randomization of sites will be stratified by US region to increase likelihood that the two groups are similar at baseline.

Patients will be enrolled by members of the Multicenter Asthma Research Collaboration (MARC), within the Emergency Medicine Network (EMNet). This research network was founded in 1996 with the original goal of performing clinical research on acute asthma. Massachusetts General Hospital is the EMNet Coordinating Center and will not participate in patient enrollment. Patient inclusion criteria include: acute asthma (i.e., fulfill American Thoracic Society criteria for asthma; age 18-54 years (to minimize contamination by COPD and to permit testing of effect modification by age); decision by ED attending to discharge patient to home on short course of systemic corticosteroids (to "validate" that patient truly had an asthma exacerbation); and informed consent. Patient exclusion criteria include: prior diagnosis of COPD, use of systemic corticosteroids in the past 2 weeks (to avoid enrollment of severe persistent asthma or patients presenting to ED with an acute asthma relapse, rather than their index presentation of acute asthma); comorbid complications (e.g., concurrent pneumonia); lack of a working cell phone and working email address (having both is common today and will increase follow-up rates); expected lack of availability for text and/or telephone follow-up at approximately 3, 6, and 12 weeks after the ED visit; or prior enrollment in this study.

All patients will undergo a short, structured interview in the ED and a focused ED chart review, using previously developed instruments for ED-based asthma research. Site investigators will enter these data into a REDCap database created and managed at the EMNet Coordinating Center in Boston. Based on their random site assignment (intervention vs usual care), intervention sites will put enrolled patients on a short course of systemic corticosteroids (e.g., prednisone 50 mg daily x 5 days) and Airsupra PRN (rescue inhaler). Usual care sites will manage patients per usual care. All patients will receive a brief educational handout about asthma.