A Remote Intervention to Prevent Overdose Among People Who Use Stimulants and/or Opioids

This Type 1 hybrid effectiveness-implementation randomized controlled trial aims to address the United States overdose crisis driven by fentanyl and other synthetic opioids. Extant studies of overdose prevention programs are limited to single cities or regions and enroll from brick-and-mortar sites, with no national, fully remote RCTs to date, and it remains unknown whether education alone drives behavior change independent of access. This study will be the first national, fully remote trial to isolate the independent impact of remote education on overdose outcomes. This project adapts our opioid overdose education and naloxone distribution intervention using a human-centered design approach, leveraging community partnerships to co-create a fully remote intervention focused on overdose prevention strategies. Access to overdose prevention resources will be made available to participants independent of this award through referral to community partners. We will use a 2×2 design crossing remote education with remote access support, isolating the individual and combined effects of these two components. The R61 phase focuses on adapting and piloting the interventions with 100 participants, assessing feasibility, acceptability, and appropriateness. The R33 phase implements a fully powered trial to compare overdose outcomes (fatal and non-fatal) among 2,952 participants randomized to four arms: education plus access support, education only, access support only, and referral only (control). All groups will receive a resource list for overdose prevention tools. The secondary outcome is knowledge of how to use the resources correctly; exploratory outcomes include protective behavioral strategies to reduce overdose risk and utilization of substance use services and treatment. The study incorporates ecological momentary assessment to elucidate daily contextual factors influencing resource use, and a cost-effectiveness analysis to identify the most cost efficient approach. Findings will directly inform scalable, low-barrier models capable of reaching rural and underserved populations not currently engaged in substance use services.