CTN-0099: Emergency Department-INitiated bupreNOrphine and VAlidaTIOn Network Trial (ED-INNOVATION)
Gail D’Onofrio, MD, MS
Lead Investigator
Yale University School of Medicine
Department of Emergency Medicine
gail.donofrio@yale.edu
David Fiellin, MD
Lead Investigator
Yale University School of Medicine
david.fiellin@yale.edu
Emergency Department (ED) initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to 7 days. This study will recruit, train, and provide resources to up to 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD.
Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment 7-days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores < 8 in a case series to potentially expand the eligibility of patients in the larger RCT to those presenting with little to no opioid withdrawal symptoms. Electronic health record (EHR) phenotypes of opioid-related illnesses will be developed and validated to characterize ED visits, better identify patients eligible for study inclusion, and facilitate future capacity for predictive analytics.
Funded by the NIH HEAL Initiative®.
Primary Findings
In this multicenter randomized clinical trial, patients presenting to the emergency department (ED) with untreated opioid use disorder (OUD) and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher were randomized to one of two groups: 7-day extended-release injectable buprenorphine or a 7-day prescription for daily sublingual buprenorphine. Engagement in OUD treatment at day 7 was the primary outcome. No difference was detected in opioid use disorder treatment engagement on day 7 between the two groups. Both buprenorphine formulations were well tolerated and precipitated withdrawal was rare despite a high prevalence of fentanyl.
Primary outcomes article: D’Onofrio G, et al. Emergency department-initiated buprenorphine for opioid use disorder: A randomized clinical trial. JAMA 2026 (in press).
Related Studies
Related Resources
Node Involvement
Lead Node(s):
All Participating Nodes: