A pragmatic, open-label, randomized trial of 1,201 patients found as-needed use of inhaled glucocorticoids plus existing therapy improved asthma outcomes in a broad population of Black and Latinx patients with poorly controlled asthma.
The Person Empowered Asthma Relief (PREPARE, NCT02995733) trial demonstrated a 15.4% lower risk of severe asthma exacerbations, reduced symptoms, and length of impairment. Data from the study was presented during the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology and simultaneously published in the New England Journal of Medicine.
Asthma imposes a significant burden on the U.S. population, with more than 3,300 asthma-attributed deaths in adults each year[1] and annual costs for adults estimated at $67 billion.[2] Black and Latinx patients bear a disproportionate share of this asthma burden,[3] [4] and efforts to reduce this disparity have mostly been unsuccessful. Earlier explanatory studies have suggested that symptom-activated use of inhaled glucocorticoids can reduce asthma attacks by up to 50% compared with usual care, while lowering inhaled glucocorticoid use by one-half or more.[5]
Of 1,201 adults (603 Black and 598 Latinx in the mainland U.S. and Puerto Rico), 600 were randomized to the intervention plus usual care group and given one-time instruction in the use of a metered-dose inhaler (beclomethasone dipropionate, 80 μg); 601 were assigned to the usual-care only group. Both groups received usual care as background therapy. Eighty-four percent of the participants were women. Twenty sites enrolled participants. Investigators used monthly surveys to follow the adult participants for up to 15 months. The primary endpoint was the annualized rate of severe asthma exacerbations.
The intervention group had a significantly lower rate of severe asthma exacerbations, with an annualized rate of 0.69, compared with 0.82 in the group receiving usual care. Measures of asthma control, quality of life, and missed days of work, school, or usual activities improved significantly in the group receiving the intervention than in those receiving usual care alone. Serious adverse events occurred in 12% of the participants, with an even distribution between the two groups. Cost implications for the intervention arm were modest, requiring an average of only 1.1 additional inhalers per year.
Patients partnered with the PREPARE team to provide input on outcome selection, study design, and the dissemination of results.
“This was a ground-breaking, randomized pragmatic trial in this ethnically diverse and underserved asthma population, and may help reduce care disparities,” said DCRI’s Frank W. Rockhold, PhD (pictured right), professor of biostatistics and bioinformatics and principal investigator of the DCRI Data Coordinating Center which performed the statistical analysis. “The promising results – based on questionnaires and hard endpoints, including asthma-related hospital admissions – showed remarkable consistency over the study period. The 94%, compliance with completion of the questionnaires was extremely high and contributed to this consistency.”
“An interesting feature of this pragmatic trial was the ease of collection of data through a website, without the need for repeated site visits,” said lead statistician Lilin She, PhD, DCRI senior biostatistician. “This enabled the study to continue without interruption even after the COVID-19 pandemic began. Including repeated events, rather than just tracking time to first event, made the statistical analysis more challenging, but gave a more comprehensive picture of patient outcomes.”
The study was funded by the Patient-Centered Outcomes Research Institute (PCORI) and others. Brigham and Women’s Hospital is the coordinating center for the study and summarized the findings in a recent press release. Previous papers described the study design and early findings.
Michael Pencina, PhD, Duke School of Medicine’s Vice Dean for Data Science & Information Technology, and Karen Chiswell, PhD, DCRI statistical research scientist, also played key roles in the study design and statistical analysis.
[1] Centers for Disease Control and Prevention. Most recent national asthma data (https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm)
[2] Nurmagambetov T, Kuwahara R, Garbe P. The economic burden of asthma in the United States, 2008–2013. Ann Am Thorac Soc 2018;15:348-56. [PMID: 29323930]
[3] Leong AB, Ramsey CD, Celed n JC. The challenge of asthma in minority populations. Clin Rev Allergy Immunol 2012;43:156-83. [PMID: 21538075]
[4] Gold DR, Wright R. Population disparities in asthma. Annu Rev Public Health 2005;26:89-113. [PMID: 15760282]
[5] https://clinicaltrials.gov/ct2/show/NCT02995733?term=02995733&draw=2&rank=1