Early emergency department experience with 7-day extended-release injectable buprenorphine for opioid use disorder.

As the opioid overdose epidemic escalates, there is an urgent need for treatment innovations to address both patient and clinician barriers when initiating buprenorphine in the emergency department (ED). These include insurance status, logistical challenges such as the ability to fill a prescription and transportation, concerns regarding diversion, and availability of urgent referral sites. Extended-release buprenorphine (XR-BUP) preparations such as a new 7-day injectable could potentially solve some of these issues. We describe the pharmacokinetics of a new 7-day XR-BUP formulation and the feasibility of its use in the ED setting. We report our early experiences with this medication (investigational drug CAM2038), in the context of an ongoing clinical trial entitled Emergency Department-Initiated BUP VAlidaTION (ED INNOVATION), to inform emergency clinicians as they consider incorporating this medication into their practice. The medication was approved by the European Medicines Agency in 2018 and the U.S. Food and Drug Administration in 2023 for those 18 years or older for the treatment of moderate to severe opioid use disorder (OUD). We report our experience with approximately 800 ED patients with OUD who received the 7-day XR-BUP preparation in the ED between June 2020 and July 2023.

Implementation Facilitation to Promote Emergency Department-Initiated Buprenorphine for Opioid Use Disorder.

Importance: Emergency department (ED)-initiated buprenorphine for the treatment of opioid use disorder (OUD) is underused. Objective: To evaluate whether provision of ED-initiated buprenorphine with referral for OUD increased after implementation facilitation (IF), an educational and implementation strategy. Design, Setting, and Participants: This multisite hybrid type 3 effectiveness-implementation nonrandomized trial compared grand rounds with IF, with pre-post 12-month baseline and IF evaluation periods, at 4 academic EDs. The study was conducted from April 1, 2017, to November 30, 2020. Participants were ED and community clinicians treating patients with OUD and observational cohorts of ED patients with untreated OUD. Data were analyzed from July 16, 2021, to July 14, 2022. Exposure: A 60-minute in-person grand rounds was compared with IF, a multicomponent facilitation strategy that engaged local champions, developed protocols, and provided learning collaboratives and performance feedback. Main Outcomes and Measures: The primary outcomes were the rate of patients in the observational cohorts who received ED-initiated buprenorphine with referral for OUD treatment (primary implementation outcome) and the rate of patients engaged in OUD treatment at 30 days after enrollment (effectiveness outcome). Additional implementation outcomes included the numbers of ED clinicians with an X-waiver to prescribe buprenorphine and ED visits with buprenorphine administered or prescribed and naloxone dispensed or prescribed. Results: A total of 394 patients were enrolled during the baseline evaluation period and 362 patients were enrolled during the IF evaluation period across all sites, for a total of 756 patients (540 [71.4%] male; mean [SD] age, 39.3 [11.7] years), with 223 Black patients (29.5%) and 394 White patients (52.1%). The cohort included 420 patients (55.6%) who were unemployed, and 431 patients (57.0%) reported unstable housing. Two patients (0.5%) received ED-initiated buprenorphine during the baseline period, compared with 53 patients (14.6%) during the IF evaluation period (P < .001). Forty patients (10.2%) were engaged with OUD treatment during the baseline period, compared with 59 patients (16.3%) during the IF evaluation period (P = .01). Patients in the IF evaluation period who received ED-initiated buprenorphine were more likely to be in treatment at 30 days (19 of 53 patients [35.8%]) than those who did not 40 of 309 patients (12.9%; P < .001). Additionally, there were increases in the numbers of ED clinicians with an X-waiver (from 11 to 196 clinicians) and ED visits with provision of buprenorphine (from 259 to 1256 visits) and naloxone (from 535 to 1091 visits). Conclusions and Relevance: In this multicenter effectiveness-implementation nonrandomized trial, rates of ED-initiated buprenorphine and engagement in OUD treatment were higher in the IF period, especially among patients who received ED-initiated buprenorphine. Trial Registration: ClinicalTrials.gov Identifier: NCT03023930.

The design and conduct of a randomized clinical trial comparing emergency department initiation of sublingual versus a 7-day extended-release injection formulation of buprenorphine for opioid use disorder: Project ED Innovation.

ED-INNOVATION (Emergency Department-INitiated bupreNOrphine VAlidaTION) is a Hybrid Type-1 Implementation-Effectiveness multisite emergency department (ED) study funded through The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM efforts to increase access to medications for opioid use disorder (OUD). We use components of Implementation Facilitation to enhance adoption of ED-initiated buprenorphine (BUP) at approximately 30 sites. Subsequently we compare the effectiveness of two BUP formulations, sublingual (SL-BUP) and 7-day extended-release injectable (CAM2038, XR-BUP) in a randomized clinical trial (RCT) of approximately 2000 patients with OUD on the primary outcome of engagement in formal addiction treatment at 7 days. Secondary outcomes assessed at 7 and 30 days include self-reported opioid use, craving and satisfaction, health service utilization, overdose events, and engagement in formal addiction treatment (30 days) and receipt of medications for OUD (at 7 and 30 days). A sample size of 1000 per group provides 90% power at the 2-sided significance level to detect a difference in the primary outcome of 8% and accommodates a 15% dropout rate. We will compare the cost effectiveness of the two treatments on the primary outcome using the incremental cost-effectiveness ratio. We will also conduct an ancillary study in approximately 75 patients experiencing minimal to no opioid withdrawal who will undergo XR-BUP initiation. If the ancillary study demonstrates safety, we will expand the eligibility criteria for the RCT to include individuals with minimal to no opioid withdrawal. The results of these studies will inform implementation of ED-initiated BUP in diverse EDs which has the potential to improve treatment access.

Barriers and Facilitators to Clinician Readiness to Provide Emergency Department-Initiated Buprenorphine.

Importance: Treatment of opioid use disorder (OUD) with buprenorphine decreases opioid use and prevents morbidity and mortality. Emergency departments (EDs) are an important setting for buprenorphine initiation for patients with untreated OUD; however, readiness varies among ED clinicians. Objective: To characterize barriers and facilitators of readiness to initiate buprenorphine for the treatment of OUD in the ED and identify opportunities to promote readiness across multiple clinician types. Design, Setting, and Participants: Using data collected from April 1, 2018, to January 11, 2019, this mixed-methods formative evaluation grounded in the Promoting Action on Research Implementation in Health Services framework included 4 geographically diverse academic EDs. Attending physicians (n = 113), residents (n = 107), and advanced practice clinicians (APCs) (n = 48) completed surveys electronically distributed to all ED clinicians (n = 396). A subset of participants (n = 74) also participated in 1 of 11 focus group discussions. Data were analyzed from June 1, 2018, to February 22, 2020. Main Outcomes and Measures: Clinician readiness to initiate buprenorphine and provide referral for ongoing treatment for patients with OUD treated in the ED was assessed using a visual analog scale. Responders (268 of 396 [67.7%]) were dichotomized as less ready (scores 0-6) or most ready (scores 7-10). An ED-adapted Organizational Readiness to Change Assessment (ORCA) and 11 focus groups were used to assess ratings and perspectives on evidence and context-related factors to promote ED-initiated buprenorphine with referral for ongoing treatment, respectively. Results: Among the 268 survey respondents (153 of 260 were men [58.8%], with a mean [SD] of 7.1 [9.8] years since completing formal training), 56 (20.9%) indicated readiness to initiate buprenorphine for ED patients with OUD. Nine of 258 (3.5%) reported Drug Addiction Treatment Act of 2000 training completion. Compared with those who were less ready, clinicians who were most ready to initiate buprenorphine had higher mean scores across all ORCA Evidence subscales (3.50 [95% CI, 3.35-3.65] to 4.33 [95% CI, 4.13-4.53] vs 3.11 [95% CI, 3.03-3.20] to 3.60 [95% CI, 3.49-3.70]; P < .001) and on the Slack Resources of the ORCA Context subscales (3.32 [95% CI, 3.08-3.55] vs 3.0 [95% CI, 2.87-3.12]; P = .02). Barriers to ED-initiated buprenorphine included lack of training and experience in treating OUD with buprenorphine, concerns about ability to link to ongoing care, and competing needs and priorities for ED time and resources. Facilitators to ED-initiated buprenorphine included receiving education and training, development of local departmental protocols, and receiving feedback on patient experiences and gaps in quality of care. Conclusions and Relevance: Only a few ED clinicians had a high level of readiness to initiate buprenorphine; however, many expressed a willingness to learn with sufficient supports. Efforts to promote adoption of ED-initiated buprenorphine will require clinician and system-level changes.

Implementation facilitation to promote emergency department-initiated buprenorphine for opioid use disorder: protocol for a hybrid type III effectiveness-implementation study (Project ED HEALTH).

BACKGROUND: Patients with opioid use disorder (OUD) frequently present to the emergency department (ED) after overdose, or seeking treatment for general medical conditions, their addiction, withdrawal symptoms, or complications of injection drug use, such as soft tissue infections. ED-initiated buprenorphine has been shown to be effective in increasing patient engagement in treatment compared with brief intervention with a facilitated referral or referral alone. However, adoption into practice has lagged behind need. To address this implementation challenge, we are evaluating the impact of implementation facilitation (IF) on the adoption of ED-initiated buprenorphine for OUD into practice. METHODS: This protocol describes a study that is being conducted through the National Institute on Drug Abuse's Center for the Clinical Trials Network. A hybrid type III effectiveness-implementation study design is used to evaluate the effectiveness of a standard educational dissemination strategy versus IF on implementation (primary) and effectiveness (secondary) outcomes in four urban, academic EDs. Sites start with a standard 60-min "Grand Rounds" educational intervention describing the prevalence of ED patients with OUD, the evidence for opioid agonist treatment and for innovative interventions with ED-initiated buprenorphine; followed by a 1-year baseline evaluation period. Using a modified stepped wedge design, sites are randomly assigned to the IF intervention which is guided by the Promoting Action on Research Implementation in Health Services (PARiHS) framework to assess evidence, context, and facilitation-related factors impacting the adoption of ED-initiated buprenorphine. During the 6 months of IF through the 1-year IF evaluation period, external facilitators work with local stakeholders to tailor and refine a bundle of activities to meet the site's needs. The primary analyses compare the baseline evaluation period to the IF evaluation period (n = 120 patients with untreated OUD enrolled during each period) on (1) rates of provision of ED-initiated buprenorphine by ED providers with referral for ongoing medication (implementation outcome) and (2) rates of patient engagement in addiction treatment on the 30th day after the ED visit (effectiveness outcome). Finally, we will perform a cost-effectiveness analysis (CEA) to determine if the effectiveness benefits are worth the additional costs. DISCUSSION: Results will generate novel information regarding the impact of IF as a strategy to promote ED-initiated buprenorphine. TRIAL REGISTRATION: ClinicalTrials.gov NCT03023930 first posted 1/10/2017, https://clinicaltrials.gov/ct2/show/NCT03023930?term=0069&rank=1.