Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Homelessness and Treatment Outcomes Among Black Adults With Opioid Use Disorder: A Secondary Analysis of X:BOT.

OBJECTIVE: We sought to identify the sociodemographic and clinical characteristics associated with homelessnesss, and explore the relationship between homelessnesss and treatment outcomes among Black individuals. METHODS: This is a secondary analysis of the subgroup of Black participants (n = 73) enrolled in "X:BOT," a 24-week multisite randomized clinical trial comparing the effectiveness of extended-release naltrexone versus sublingual buprenorphine-naloxone (n = 570). Outcomes included medication initiation, return to extramedical use of opioids assessed by both self-report and urine toxicology, and engagement in medications for opioid use disorder (MOUD) treatment at 28 weeks postrandomization. Descriptive statistics were performed. RESULTS: Black participants were mostly unmarried and male, and about a third were aged 21-30 years. Among people experiencing homelessnesss, more were uninsured (45.5% [10/22] vs 19.6% [10/51]), unemployed (77.3% [17/22] vs 64.7% [33/51]), and reported alcohol (40.9% [9/22] vs 23.5% [12/51]) and sedative use (54.5% [12/22] vs 17.6% [9/51]) within the previous 30 days. Compared with housed Black individuals, a slightly higher proportion of Black individuals experiencing homelessnesss successfully initiated study medication (81.1% [18/22] vs 72.6% [37/51]); similar proportions returned to opioid use during the trial (68.2% [15/22] vs 68.6% [35/51]) and were engaged in MOUD at 28 weeks after trial entry (72.2% [13/18] vs 69.7% [23/33]) among participants located for follow-up. CONCLUSIONS: These descriptive results among Black patients participating in a trial of MOUD suggest that efficacious MOUD is possible despite homelessnesss with additional clinical supports such as those provided by a clinical trial.

Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.

BACKGROUND: Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. METHODS: The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. DISCUSSION: If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. TRIAL REGISTRATION: NCT04762537 Registered February 21, 2021.

Patient Characteristics Associated with Opioid Abstinence after Participation in a Trial of Buprenorphine versus Injectable Naltrexone.

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Social Network Intervention Reduces Added Sugar Intake Among Baltimore Public Housing Residents: A Feasibility Study.

Public housing residents have high intake of added sugars, which is associated with sugar-sweetened beverage (SSB) consumption in their social networks. In this feasibility study, we designed and tested a network-oriented intervention to decrease added sugar intake by encouraging reduced SSB consumption. We conducted a 6-month single-arm trial testing a small-group curriculum (9 sessions) that combined behavior change strategies to reduce added sugar intake by promoting SSB reduction with a peer outreach approach. We recruited and trained public housing residents to be "Peer Educators," who then communicated information and made changes to reduce SSB with their network members. We calculated the median number of group sessions attended and determined the percentage of individuals satisfied with the program. We estimated added sugar intake using a 5-factor dietary screener and compared baseline and 6-month median values using Wilcoxon signed rank tests. We recruited 17 residents and 17 of their network members (n = 34). Mean age was 45.7 years, 79.4% were women, and 97.1% were African American. Median number of sessions attended was 9 (interquartile range: 4-9), and 88.2% were very satisfied with the program. Overall, baseline median added sugar intake was 38.0 tsp/day, which significantly declined to 17.2 tsp/day at 6 months (P < .001). Residents and network members achieved similar results at 6 months (17.4 vs 16.9 tsp/day, respectively). In conclusion, our results demonstrate that a social network intervention aimed at reducing SSB consumption is feasible and can produce significant decreases in adult added sugar intake, which warrants further investigation in a randomized controlled trial.

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts.

We performed a prospective, 12-month, single-center, nonrandomized, open-label pilot study to investigate the use of belatacept therapy combined with alemtuzumab induction in renal allografts with preexisting pathology, as these kidneys may be more susceptible to additional toxicity when exposed to calcineurin inhibitors posttransplant. Nineteen belatacept recipients were matched retrospectively to a cohort of tacrolimus recipients on the basis of preimplantation pathology. The estimated glomerular filtration rate was not significantly different between belatacept and tacrolimus recipients at either 3 or 12 months posttransplant (59 vs 45, P = 0.1 and 56 vs 48 mL/min/1.72/m2 , P = 0.3). Biopsy-proven acute rejection rates at 12 months were 26% in belatacept recipients and 16% in tacrolimus recipients (P = 0.7). Graft survival at 1 year was 89% in both groups. Alemtuzumab induction combined with either calcineurin inhibitor or costimulatory blockade therapies resulted in similar acceptable one-year outcomes in kidneys with preexisting pathologic changes. Longer-term follow-up may be necessary to identify preferential strategies to improve outcomes of kidneys at a higher risk for poor function (ClinicalTrials.gov-NCT01496417).