Extended Intervention for Tobacco Use (EXIT) for people experiencing homelessness: study protocol for a randomized controlled trial

Abstract Background Approximately 70% of people experiencing homelessness smoke cigarettes, compared to 9.9% in the US general population. Barriers to quitting and sustaining cessation include structural inequities (e.g., lack of housing; limited treatment access), and high rates of serious mental illness and substance use disorders. Existing cessation treatments are often brief, not integrated into community service settings, and lack ongoing behavioral support. Community pharmacies represent a promising strategy to expand access to evidence-based tobacco treatment; however, this approach has primarily been tested in short-duration interventions. We developed the Extended Intervention for Tobacco Use (EXIT), which links extended pharmacotherapy with wellness-focused telephone coaching. This protocol describes a randomized controlled trial evaluating the feasibility, acceptability, and preliminary efficacy of EXIT. Methods This two-arm, parallel-group randomized controlled trial will be conducted in transitional shelters in Los Angeles and San Francisco. We will enroll 150 adults experiencing homelessness who smoke at least five cigarettes per day (expired carbon monoxide [CO] ≥ 8 ppm) and intend to quit within six months. Participants will be randomized 1:1 to EXIT or a pharmacist-only comparator condition (“pharm-only”). The pharm-only condition includes a single pharmacist-delivered 5As telephone session and three months of nicotine replacement therapy (NRT). The EXIT intervention includes a 5As session, six months of NRT, and 14 wellness-focused telephone coaching sessions delivered over six months by trained health coaches. The primary outcome is adherence, measured by the number of coaching sessions attended and adherence to NRT. Secondary outcomes include biochemically verified 7-day point prevalence abstinence at 3 and 6 months (CO ≤ 5 ppm). Assessments occur at baseline, 1, 3, and 6 months and include tobacco use, nicotine dependence, health behaviors (e.g., diet; physical activity), mental health, substance use, and NRT adherence. Discussion This study evaluates the first known intervention that pairs extended-duration pharmacotherapy with wellness-focused telephone coaching within transitional shelters. By integrating tobacco treatment into homeless services and pharmacy infrastructure, EXIT is designed to reduce structural barriers to sustained cessation. Findings will inform a future fully powered trial to provide a scalable model for delivering tobacco cessation treatment to people experiencing homelessness. Trial registration ClinicalTrials.gov #: NCT07148232; Registration date: 2025-08-22.