Drug Use After Emergency Department-Initiated Injectable Buprenorphine: A Secondary Analysis of the ED-INNOVATION Ancillary Safety and Feasibility Trial

Study Objective: To characterize opioid and nonopioid drug use in the week following emergency department (ED)-initiated extended-release buprenorphine (XR-BUP) treatment using both self-reported data and urine drug screens (UDS). Methods: This study uses data collected during a nonrandomized clinical trial of patients with untreated opioid use disorder (OUD), testing the safety and feasibility of initiating XR-BUP in patients presenting with minimal to mild withdrawal. The study was conducted from July 2020 to May 2023 across four urban academic EDs in the Northeast, Mid-Atlantic, and Pacific regions of the United States. A total of 100 participants, 18 years or older with OUD defined by DSM-5 criteria, a clinical opiate withdrawal scale (COWS < 8), and a positive opioid urine screen were included. Individuals with recent MOUD treatment, presentation for overdose, or concurrent methadone use were excluded. All participants received a single subcutaneous injection of 24 mg XR-BUP (CAM2038) during their ED visit. The primary outcomes were self-reported daily opioid and nonopioid drug use over 7 days postinjection using daily Qualtrics surveys and UDS results on day 7. Results: Among participants who received XR-BUP and completed daily surveys, 98% reported at least one opioid-free day, and 63% reported no opioid use across all 7 days. Day 7 UDS results showed decreased detection of opioids, stimulants, and benzodiazepines. Reported polysubstance use also declined over the observation period. Conclusions: ED-initiated XR-BUP was associated with substantial reductions in opioid and polysubstance use during the first week post-discharge, supporting its role in early overdose risk mitigation and highlighting its value as an ED-based intervention for opioid use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT03658642.