Twenty-five million people have asthma in the United States, with over 45% experiencing one or more exacerbations (worsening of symptoms that disrupts their lives) per year. Asthma exacerbations cause many lost days from school or work and account for over 3,500 deaths per year. Guidelines support the use of inhaled corticosteroids as part of rescue therapy, most commonly as Single Maintenance and Reliever Therapy (SMART). Long-term (>6 months) therapy with azithromycin (a macrolide antibiotic) has demonstrated similar reductions in asthma exacerbations to SMART therapy. Asthma is recognized as including clinical and biological variations. Which variations respond best to SMART versus azithromycin is not clear. Furthermore, the two have not been studied when used together.
The Individualizing Treatment for Asthma in Primary Care study will be a four-arm study with 3,200 people. Treatment will vary randomly at the patient level. Study arms will be SMART therapy versus azithromycin therapy versus SMART plus azithromycin versus control. All participants will be asked to record their asthma symptoms using home monitoring tools. The primary outcome will be yearly asthma exacerbation rates compared across the three intervention arms to the control arm. Secondary outcomes will be asthma control (Asthma Control Test or ACT) and asthma quality of life (mini-Asthma Quality of Life Questionnaire.) To study the impact of asthma variations, the analyses will include total blood eosinophil counts, infectious biomarkers for Mycoplasma pneumoniae and Chlamydia pneumoniae, smoking status, health literacy, onset of asthma associated with a lower respiratory tract infection, and Black/African American race. The project team hypothesizes that all treatment arms will be better than the control arm. The project team hypothesizes that SMART therapy will work better in non-smokers or those with high total blood eosinophil counts or in people with lower health literacy. The project team hypothesizes that azithromycin will work better in smokers or individuals with an associated lower respiratory tract infection at the time their asthma began or with selected positive biomarkers.
Participants will come from primary care practices from across the United States. Participants must have an asthma diagnosis for at least one year, be at least 12 years old, and under 76 years old. They must have had an exacerbation requiring steroid pills or shots or a hospitalization in the past 12 months or have an ACT score less than 20. After consent, participants will complete surveys every other month for 16 months. Possible exacerbations will be validated by clinicians who do not know the treatment arm of the participant. People who experience three exacerbations in less than 12 months will have treatments increased if not already in the dual treatment arm. People in the control arm will move to SMART therapy while people in either single therapy will move to dual therapy. These participants would be followed for an additional 12 months. Individuals who finish either of the azithromycin arms will be offered six additional months of follow up after stopping the azithromycin only. How well participants and people in the practices are able to carry out the study will be tracked using an approach called PRISM/RE-AIM.
The analyses will be based on a model called the Negative Binomial distribution. In addition to treatment arms, the analysis will assess the impact of sex, race, smoking history, asthma treatment at enrollment, total eosinophil count, and ability to use mobile technology, as well as the effect of the organization and practice on the outcomes. The variations of treatment effect will use the same approach as the main analysis with a focus on interactions between the treatments the covariates.
Study results can be used by clinicians and patients to identify appropriate treatment for patients based on their individual characteristics, and by insurers to determine what types of therapy to pay for.
Stakeholders are integral members of the study team with decision making authority. Stakeholder groups including 1) patients and caregivers, 2) patient advocacy groups, 3) clinicians (physicians, nurses, and pharmacists), 4) professional societies, 5) healthcare policy experts, 6) payers, 7) asthma experts and researchers, and 8) site research teams have been engaged in formulating the research questions, identifying the study groups, selecting the interventions, choosing outcomes, and suggesting the exploratory aims and analyses
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.