Search the Library
Enter keywords and hit Enter (or click the magnifying glass) to search. You can then also select document type or subject/topic to narrow results further (or just use those for searching without a keyword). Results display below this search form.
Document types
Subjects
Use:
"exact phrase" word1 -word2 (finds word 1 NOT word2) word1 word2 (finds both words)
Results:
Title opens document
“Show details” reveals abstract & other info
Checkboxes select items for copy/pasting or printing
Search results
Importance: Health plan disenrollment may interrupt treatment for opioid use disorder (OUD) and overall care, increasing risk for serious outcomes, including overdose and death. There is limited evidence on the association of disenrollment with all-cause and overdose mortality after initiating medications for OUD (MOUD) treatment.
Objective: To assess the association of health plan disenrollment with all-cause and overdose mortality in patients treated with MOUD.
Design, setting, and participants: This cohort study conducted by the CTN Health Systems Node, included privately and publicly insured patients aged 16 years or older who initiated buprenorphine or naltrexone for OUD treatment between January 1, 2012, and December 31, 2021, at 3 integrated health insurance and care delivery systems in 2 US states. Patients were followed up to 2 years until December 31, 2022. Data were analyzed July 2024 to November 2025.
Exposure: Health plan disenrollment following MOUD initiation.
Main outcomes and measures: All-cause mortality and drug-related and alcohol-related overdose mortality within 2 years of MOUD initiation ascertained from the National Death Index. Survival analyses were adjusted for patient sociodemographic and clinical characteristics.
Results: Among 20,011 patients (mean [SD] age 38.7 [15.1] years; 12 299 males [61.5%]) who were treated for OUD, 6948 (34.7%) experienced disenrollment and 586 (2.9%) died during follow-up. The crude rate was 15.3 (95% CI, 14.1-16.6) per 1000 person-years for all-cause mortality and 6.2 (95% CI, 5.4-7.0) per 1000 person-years for overdose mortality. Ever experiencing disenrollment showed elevated all-cause mortality (17.6 [95% CI, 14.9-20.8] vs 14.7 [95% CI, 13.4-16.1] per 1000 person-years) and overdose mortality (8.9 [95% CI, 7.1-11.3] vs 5.4 [95% CI, 4.7-6.3] per 1000 person-years) relative to remaining enrolled. In adjusted analyses, ever experiencing disenrollment was associated with increased hazards of all-cause (hazard ratio [HR], 1.51; 95% CI, 1.23-1.84) and overdose mortality (HR, 1.56; 95% CI, 1.17-2.09). Compared with remaining enrolled and receiving MOUD treatment, being disenrolled (HR, 4.34; 95% CI, 3.19-5.89) and being enrolled and not receiving MOUD treatment (HR, 4.19; 95% CI, 3.24-5.43) were associated with overall mortality.
Conclusions and relevance: In this cohort study of patients who initiated MOUD, experiencing health plan disenrollment was associated with increased mortality risk compared with remaining enrolled. Strategies are needed to improve continuity of health coverage and mitigate the elevated mortality risk during insurance transitions for patients receiving medications for OUD.
Background and aims: Despite similar substance use levels, Black adults experience greater family, legal, employment and other social-contextual challenges related to recovery than other groups. Substance use treatments that address both substance use and social-contextual factors are uniquely positioned to address these substance-related problems and produce more sustainable improvements in social functioning than treatment as usual (TAU) or behavioral controls (Control). The aim of this study was to evaluate changes in substance-related problems among Black adults, focusing on the comparative effectiveness between social-contextual treatments and TAU/Control.
Design: Individual-level data synthesis based on secondary analysis of Black adults enrolled in the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN).
Setting: All data were collected in the primary studies between 2001 and 2008 at clinics across the United States.
Participants: Black adults who reported cocaine and/or opioid use across nine studies within the NIDA CTN. The sample used herein consisted of individuals from five of these studies who provided data on substance-related problems (n=532; mean age=39.34; standard deviation=9.6).
Measurements: There were two treatment conditions: Social-contextual (e.g. Motivational Interviewing, Seeking Safety, STAGE 12) and TAU/Control. Moderated nonlinear factor analysis estimated latent scores for substance-related problems, using subscales from the Addiction Severity Index, while accounting for measurement noninvariance across studies, time and covariates. Linear mixed models estimated latent score differences over time between social-contextual treatments and TAU/Control during treatment and from the end of treatment through 12-month follow-up.
Findings: Both treatment groups improved across substance-related problem areas from baseline to the end-of-treatment (Cohen’s d = -0.10 to d = -0.47), with effects maintained at 12-month follow-up. Although social-contextual treatments did not statistically significantly outperform TAU/Control from baseline to end-of-treatment, they showed greater effects from end of treatment to 12-month follow-up in family/social [Cohen’s d difference ( d) = -0.47, 95% confidence interval (CI) = -0.57 to -0.38], legal ( d = -0.20, 95% CI = -0.31 to -0.10) and psychiatric problems ( d = 0.29, 95% CI = -0.38 to -0.20) than TAU/Control. Sensitivity analyses indicated that Seeking Safety and STAGE 12 predominantly drove post-treatment improvements in family/social problems.
Conclusions: Substance use treatment may yield broader, delayed benefits beyond substance use reduction among Black adults in the United States. Compared with treatment-as-usual, social-contextual treatments can yield more sustainable effects in legal, family and psychiatric areas among Black adults, with interventions such as Seeking Safety and STAGE 12 showing particular benefits in addressing family-related challenges.
Related protocols: CTN-0125
Background and aim: Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial.
Methods: Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success.
Results: 204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89).
Conclusions: Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.
Related protocols: CTN-0051
Medications for opioid use disorder (MOUD), such as methadone, buprenorphine, and extended-release naltrexone (XR-NTX), have been shown to reduce or eliminate opioid use and craving, protecting against opioid overdose and death. Stopping medication is associated with risk of relapse and potential overdose. Unsurprisingly, patients may desire to stop MOUD because of adverse effects, burden, or preference for recovery without medication, asking, “How long do I need to take medication?” Clinicians who treat OUD often encounter this uncomfortable risk-benefit discussion with patients who want to stop MOUD, hoping that the patients can do so successfully, while acknowledging the major risks. Prospective data are needed to inform those discussions. In designing one of the first clinical trials focused on MOUD discontinuation—the Discontinuation Phase of the Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD) trial (NCT04464980)2—the investigators identified ethical issues that needed consideration in designing the study.
The authors of this Viewpoint are study investigators, including a social worker (S.E.P.) and 2 psychiatrists experienced with MOUD (R.D.W. and E.V.N.). In this Viewpoint, we describe those ethical challenges and our attendant solutions to inform the design of other studies of medication discontinuation, where discontinuing treatment could have grave consequences.
Related protocols: CTN-0100
Background: Rural communities continue to experience high overdose mortality rates and challenges retaining individuals with opioid use disorder (OUD) on medications for opioid use disorder (MOUD). The most recent formulation of injectable extended-release buprenorphine (XR-BUP) may improve treatment engagement and outcomes for people with OUD.
Objectives: The RXR study (CTN-0102-XR) aims to evaluate the feasibility of implementing XR-BUP in rural settings, acceptability of XR-BUP to clinic staff and patients, and effectiveness of XR-BUP compared with sublingual buprenorphine-naloxone (SL-BUP).
Study design and methods: This is an open-label randomized controlled trial (RCT) using intention-to-treat (ITT) analysis. Approximately 144 participants recruited from seven rural clinic sites will be randomized to receive XR-BUP or SL-BUP in a ratio of 2:1, and will receive study medication for 14 weeks. Participants in the XR-BUP condition will receive two weekly initiation dosages, followed by the target monthly dosage (128 mg) at Weeks 2, 6, and 10. Participants in the SL-BUP condition will receive medication on a similar schedule, with a target dose range of 16-24 mg/day. The main comparative effectiveness outcome measure is the number of monthly opioid negative urine drug screens (UDS) for non-prescribed opioids from Weeks 2-14. Feasibility and acceptability will be evaluated using mixed methods, combining participant survey and interview data from clinic administrators, providers, and patients.
Conclusions: If demonstrated to be feasible and acceptable to participants and staff and there is evidence of effectiveness for people with OUD in reducing opioid use, XR-BUP may be considered an important option for addressing OUD in rural settings.
Related protocols: CTN-0102-XR
Background and aims: Sleep disruptions increase the risk of substance misuse. Substance use-especially stimulants-can increase acute and chronic sleep dysfunction. This study aimed to estimate the associations between sleep disturbance and stimulant use over time among participants with stimulant use disorder (StUD).
Design: In this secondary analysis, a Random Intercept Cross-Lagged Panel Model (RI-CLPM) was used to assess sleep disturbance and stimulant use over 8 weeks among participants with StUD.
Setting: United States of America.
Participants: The analysis included 793 participants with StUD enrolled across 3 randomized controlled trials in the National Institute on Drug Abuse’s Clinical Trials Network (CTN): CTN-0037, CTN-0048 and CTN-0068.
Measurements: Self-reported sleep disturbance was harmonized as a binary indicator across trial measures at each week. Stimulant use days per week were captured by Timeline Follow Back. Baseline covariates included age, sex, race/ethnicity, employment status, presence of depressive symptoms, any psychiatric history, treatment arm and trial.
Findings: Sleep disturbance was associated with a higher average number of stimulant use days the following week [β = 0.15, 95% confidence interval (CI) = 0.09, 0.22, P < 0.001], and greater stimulant use was linked to increased odds of subsequent sleep disturbance (odds ratio = 1.20, 95% CI = 1.14, 1.26, P < 0.001).
Conclusions: Higher-than-usual stimulant use appears to be associated with increased likelihood of sleep disturbance the following week, and vice versa.
Related protocols: CTN-0037, CTN-0048, CTN-0068
Importance: Hospital-based opioid treatment (HBOT) can improve outcomes for patients with opioid use disorder, but little is known about specific attributes and supports needed for clinical champions to successfully implement HBOT.
Objective: To identify characteristics and supports of effective clinical champions implementing HBOT in US hospitals.
Design, setting, and participants: Qualitative study using postimplementation semistructured interviews conducted with individuals highly involved in HBOT implementation, including champions and hospital staff at 12 US community hospitals randomized to the high-intensity group of the Exemplar Hospital Initiation Trial to Enhance Treatment Engagement, a national implementation trial comparing low- and high-intensity HBOT implementation strategies. Interviews explored implementation experiences over 24 months from December 2021 to December 2023. Interviews were audio recorded, transcribed, and coded. The framework method and in-depth thematic analysis were used to explore the role of champions.
Interventions: All hospitals received a best-practices manual, video webinar series, and hub team support for questions, while hospitals randomized to the high-intensity group also received monthly practice facilitation, telementoring, and 10% effort funding for a local champion. Champions led HBOT implementation with support from regional hubs with HBOT expertise.
Measures: Effective champions were defined as those perceived by staff to successfully lead HBOT implementation. Open-ended questions and thematic analysis explored participants’ perspectives on attributes of effective champions and how they overcame implementation barriers.
Results: A total of 31 hospital staff (15 physicians, 5 executives, 5 pharmacists, 2 nurse practitioners, 2 social workers, 1 nurse, and 1 addiction counselor) were interviewed. Effective champions were perceived as respected hospital “insiders” with institutional influence, persistence, and systems change skills. They built multidisciplinary teams, developed standard workflows, and used emotionally resonant strategies (eg, patient narratives) to overcome stigma and engage hospital leadership. Champions could be effective without addiction medicine expertise, particularly when provided with protected time, hospital leadership support, and external practice facilitation from addiction experts.
Conclusions and relevance: This multisite qualitative study underscores the vital role of champions in expanding hospital-based opioid care. To ensure HBOT expansion, hospitals should invest in champions, protected time, leadership backing, and external supports that legitimize and routinize evidence-based addiction care.
Related protocols: CTN-0098
Primary care is a critical setting to provide care for the 75-79% of patients who have opioid use disorder (OUD) but do not receive medications for OUD. However, patient perceptions of primary care of OUD are not well understood. Patients completed surveys about their experience with opioid-related clinical decision support system (CDSS) printouts and OUD treatment in the first 7-9 months of implementation of an OUD-CDSS. Survey responses were presented overall and by reason for study eligibility. Of 277 patients completing surveys, 22% recalled seeing the printouts; of these, 85% said the printouts made them more comfortable discussion opioid risk. Of all respondents, half discussed opioids during their visit; of these, 84% felt conversations were conducted sensitively. Overall, 88% felt primary care was the right setting to discuss opioid risks. The opioid-related printouts and discussions were generally well-received, and patients felt primary care was a suitable setting for opioid-related care.
Background: Opioid use disorder (OUD) remains a significant public health issue. Yet, few primary care clinicians (PCCs) screen for, diagnose, or treat OUD. Clinical decision support tools (CDS) integrated into the electronic health record improve process and outcome measures across a variety of conditions. We evaluated PCC perspectives on an OUD CDS tool (Opioid Wizard) deployed through a clinic-randomized trial.
Methods: This is a secondary analysis of CTN-0095, a trial evaluating the effectiveness of Opioid Wizard on OUD process and outcome measures. In short, 92 primary care clinics across three health systems were randomized to Opioid Wizard or usual care. PCCs completed online surveys pre- and 9-month post-Opioid Wizard’s go-live date. Survey items measured PCC self-reports on their confidence and ability to manage OUD, and for PCCs in Opioid Wizard clinics, perceptions about the tool. Generalized linear mixed models with Poisson distribution estimated change in survey response from baseline to follow-up within each treatment group (risk ratios) and in intervention relative to control clinics (ratio of risk ratios).
Results: 361 PCCs (n = 180 Opioid Wizard, n = 181 usual care, 63% female) answered at least one survey. Confidence in screening (RR 1.32, 95% CI 1.07, 1.62), diagnosing (RR 1.24, 95% CI 1.02, 1.50), and referring (RR 1.17, 95% CI 1.02, 1.34) patients for OUD care significantly increased in Opioid Wizard clinics only. Confidence in treating OUD with buprenorphine did not increase in either setting. Of 55 PCCs who used Opioid Wizard at least once, 80% agreed Opioid Wizard made tasks easier and 70% agreed using Opioid Wizard was time “well spent,” but only 44% were likely to recommend it to colleagues.
Conclusion: Opioid Wizard increased PCC confidence across a variety of OUD care measures yet enthusiasm for and use of the tool was limited. Efforts to increase Opioid Wizard use may improve OUD care measures.
Related protocols: CTN-0095
This is the primary outcomes article for CTN-0080. Importance: Treating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation.
Objective: To evaluate the effectiveness and safety of extended-release buprenorphine vs sublingual buprenorphine for OUD in pregnancy through 12 months post partum.
Design, setting, and participants: This 2-group, open-label, noninferiority, randomized clinical trial was conducted between July 2, 2020, and October 30, 2024, among adults with OUD and a singleton pregnancy of 6 to 30 weeks’ gestational age at 13 outpatient cross-disciplinary peripartum OUD treatment sites.
Interventions: Randomization to sublingual or extended-release buprenorphine (weekly formulation during pregnancy, monthly formulation optional post partum if not breastfeeding).
Main outcomes and measures: The primary and key secondary outcomes were illicit opioid abstinence during pregnancy and the postpartum period, respectively, defined as the proportion of weekly collected urine samples negative for illicit opioids. If noninferiority was demonstrated at a margin of 0.15, testing for superiority was planned. Key secondary infant outcomes from medical records were opioid treatment for neonatal opioid withdrawal syndrome (NOWS; yes or no) and number of opioid treatment days for NOWS.
Results: Among 140 randomized participants, the mean (SD) age was 31.2 (4.6) years. There were 10 Black participants (7.1%), 10 Hispanic participants (7.1%), 116 (82.9%) White participants, and 14 participants (10.0%) who belonged to additional groups. All but 2 were already prescribed sublingual buprenorphine. Study completion was 98% through pregnancy (137 participants) and 81% through 12 months post partum (114 participants). Illicit opioid abstinence was higher during pregnancy for participants receiving extended-release vs sublingual buprenorphine (82.5% vs 72.6%; mean difference, 9.84 [95% CI, 1.72 to 17.95] percentage points; P = .009). Postpartum abstinence rates declined and were similar in both groups (60.2% vs 59.5%; mean difference, 0.65 [98% CI, -12.72 to 14.02] percentage points; P = .45). Those receiving extended-release buprenorphine experienced fewer serious adverse events during pregnancy (8.7% vs 26.8%; P = .007) and post partum (6.0% vs 18.6%; P = .04). Nonserious adverse events rates did not differ between groups, but more were deemed medication-related for extended-release participants during pregnancy (26.1% vs 7.0%; P = .003). Infants exposed to extended-release vs sublingual buprenorphine did not differ in need for opioid treatment (30.2% vs 26.5%; relative risk, 1.14 [98% CI, 0.54 to 1.99]; P = .64) or mean (SE) treatment days (10.9 [2.2] vs 14.8 [3.0] days; relative risk, 0.73 [98% CI, 0.36 to 1.51]; P = .28). At birth, extended-release-exposed neonates had larger mean (SE) head circumferences than those exposed to sublingual buprenorphine (34.0 [0.2] vs 33.4 [0.2] cm; mean difference, 0.63 [95% CI, -0.00 to 1.26] cm; P = .049).
Conclusions and relevance: The findings of this randomized clinical trial support weekly extended-release buprenorphine for OUD treatment during pregnancy.
Related protocols: CTN-0080
Background and objectives: Patients using fentanyl have worse treatment outcomes; however, little is known about other drugs that complicate treatment.
Methods: A national survey (n = 396) was conducted for CTN-0135 using a random sample of clinicians waivered to prescribe buprenorphine in the United States. This study reports the results of a single survey item on clinicians’ perceptions of other drugs, besides IMF, complicating treatment.
Results: Clinicians reported methamphetamine (86.4%), synthetic cannabinoids (42.7%), and xylazine (41.4%) were complicating treatment; reports varied by geographic region.
Conclusions and scientific significance: Rapid clinician surveys can provide real-time data on changing patterns of drug use’s impact treatment outcomes.
Related protocols: CTN-0135
Background: Most people with opioid use disorder (OUD) do not receive evidence-based treatment. To increase treatment rates, primary care clinics may choose to implement risk prediction tools available in the electronic health record (EHR) to identify patients with a high risk of OUD or overdose.
Objective: To externally validate Epic’s cognitive computing model to predict the Risk of Opioid Abuse or Overdose (referred to as the Opioid Risk Score; ORS) in three large integrated health systems.
Design: Prospective cohort study secondary to an ongoing clinical trial.
Participants: Patients (N = 704,764) aged 18-75 who had a primary care encounter during the study period (April 2021-December 2022) and did not have an OUD diagnosis at index.
Main measures: Data were extracted from the EHR. The index date was defined as the first date within the study period where the patient met eligibility criteria and had an ORS calculated by the EHR. The binary outcome variable was whether the patient was diagnosed with OUD or experienced an opioid overdose within 12 months of the index date.
Key results: Most patients were classified as low risk on ORS (99.6%). Few patients experienced an OUD diagnosis or overdose in the 12-month follow-up period (0.3%). The model correctly classified 185 of 2362 patients who experienced an event (sensitivity 0.0783, 95% CI 0.0675, 0.0892) and 699,926 of 702,406 patients who did not experience an event (specificity 0.9965, 95% CI 0.9963, 0.9966). Few patients with high ORS experienced the event (PPV 0.0694, 95% CI 0.0598, 0.0791). The model had excellent discrimination (c-statistic = 0.815) but was poorly calibrated, underestimating risk for patients who experienced the outcomes.
Conclusions: Epic’s ORS demonstrated excellent discrimination but very low sensitivity across three large integrated health systems. Health systems should exercise caution before implementing vendor risk prediction models without validating their use in their patient populations.
Related protocols: CTN-0095
Evidence-based prevention interventions for young people have a shelf-life. When programs are revised and updated, it is unclear how much of the evidence carries over into the new edition. This presentation will review some of the challenges and opportunities associated with the recently released second edition of kiR as a case study. The updated version of kiR covers new types of drugs (e.g., vaping) and addresses co-occurring externalizing conditions (several forms of violence involvement). The original evidence was
gathered in Arizona, but kiR is being used nationwide and globally through culturally adapted versions. Additional research is needed to assess moderation of kiR program’s effects based on key participant characteristics and variations in implementation contexts across the US. The presentation will conclude by
exploring the possibility of assessing the feasibility and acceptability of the new version of kiR from multiple stakeholder viewpoints and to identify barriers and facilitators to its adoption and sustainment.
This editorial in JAMA describes the outcomes and implications of the primary outcomes paper for CTN-0099, the ED-INNOVATION trial, which compared the use of a 7-day extended-release buprenorphine injection to 7 days of sublingual buprenorphine for patients in the ED presenting with opioid use disorder and found no difference in treatment engagement at 7 days or 30 days among the two groups. They also reported low rates of precipitated withdrawal in both groups, despite a high rate of fentanyl use.
In the context of an ongoing public health emergency related to drug toxicity deaths, emergency department visits are undeniably important opportunities to identify people with high-risk opioid use and engage them in care. Increasing access to evidence-based harm reduction and treatment options for people with OUD in EDs is a crucial aspect of the response to this public health emergency.
Increasing the choices of opioid agonist therapies available in EDs is important. Providers should be careful to monitor their own biases regarding which approach might work best for an individual patient (for example, many providers might assume an injection is the easiest or best approach for a patient, while the patient may feel differently).
This study provides further evidence that EDs can and must lead ED-specific studies and initiatives that confirm best practices and increase access to lifesaving opioid agonist therapies. The way forward requires that clinician-scientists continue to foster a discussion of what is possible in EDs, while prioritizing patient-centered decision-making and consent, and clearly establishing both safety and benefit of interventions prior to implementation.
Related protocols: CTN-0099
This is the primary outcomes article for CTN-0099.
Importance: Extended-release injectable buprenorphine may expand the reach of initiating medications for opioid use disorder in high-risk and hard-to-reach individuals who visit the emergency department (ED) and can be administered in low levels of withdrawal.
Objective: To compare the effect of ED-initiated 7-day extended-release injectable buprenorphine vs sublingual buprenorphine on treatment engagement at 7 days.
Design, Setting, and Participants: Multicenter randomized clinical trial enrolling adult patients presenting to the ED with untreated opioid use disorder and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher across 29 EDs in the US from July 12, 2020, to August 21, 2024. Final follow-up was completed on October 24, 2024.
Interventions: Patients were randomized to receive a 24-mg injection of extended-release buprenorphine (equivalent to 16 mg/d) or sublingual buprenorphine, which included either self-administration instructions if the COWS score was less than 8 or administration of 8 mg of sublingual buprenorphine in the ED if the COWS score was 8 or higher. All sublingual buprenorphine group patients received a 7-day prescription for 16 mg/d. Both groups were provided referral for ongoing medication with a scheduled appointment within 7 days.
Main Outcomes and Measures: Engagement in opioid use disorder treatment on day 7 was the primary outcome. Secondary outcomes included engagement at 30 days, precipitated withdrawal and overdose events, craving scores, days of illicit opioid use, and patient satisfaction with treatment.
Results: Among 2000 patients randomized, 6 who were enrolled twice were excluded, resulting in 991 in the extended-release group and 1003 in the sublingual group. The median age was 37 (IQR, 30-47) years, 68% were male, 31% had an initial COWS score of 4 to 7, and 76% tested positive for fentanyl. The adjusted proportion of engagement in opioid use disorder treatment at 7 days was 40.5% with extended-release buprenorphine vs 38.5% with sublingual buprenorphine (adjusted difference, 1.6%; 95% CI, −2.8% to 6.0%). Engagement at 30 days was similar, with adjusted proportions of 43.8% with extended-release buprenorphine vs 44.9% with sublingual buprenorphine (adjusted difference, −1.5%; 95% CI, −6.2% to 3.2%). Precipitated withdrawal was rare: 6 (0.6%) with extended-release buprenorphine and 8 (0.8%) with sublingual buprenorphine. Overdose events within 30 days occurred in 18 participants (2.3%) in each group. Patients receiving extended-release buprenorphine reported lower mean craving scores at 7 days vs those receiving sublingual buprenorphine (scale, 0-100; mean score, 26.5 vs 30.2, respectively; adjusted mean difference, −3.85; 95% CI, −7.08 to −0.63), fewer days of illicit opioid use in the past 7 days (adjusted ratio of means, 0.77; 95% CI, 0.68-0.95), and better treatment satisfaction scores (scale, 1-5; adjusted mean difference, 0.13; 95% CI, 0.01-0.25).
Conclusions and Relevance: No difference was detected in opioid use disorder treatment engagement on day 7 between the 7-day extended-release and sublingual buprenorphine groups. Both buprenorphine formulations were well tolerated; precipitated withdrawal was rare despite a high prevalence of fentanyl.
Related editorial: Moe J, et al. Buprenorphine in the ED — Balancing access, safety, and autonomy. JAMA 2026 (in press).
Related protocols: CTN-0099