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Abstract: 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

Abstract:

Introduction: Hospitalizations are common among people with opioid use disorder (OUD). While hospitalizations represent opportunities to engage patients and offer treatment, they are also destabilizing events associated with an increased risk of death in the post-hospitalization period.

Methods: We conducted a retrospective cohort study within the Veterans Health Administration including all Veterans with OUD who experienced at least one medical hospitalization between January 2011 and December 2021 (part of CTN-0087). We examined which patient-level clinical and demographic factors were associated with all-cause and opioid-related mortality within 0-30 and 0-365 days following an index medical hospitalization.

Results: The cohort included 90,920 Veterans with OUD who experienced one or more medical hospitalizations during the study period. Median age was 58 years, and 93% were male. Older age (adjusted Odds Ratio [aOR] range 30d: 1.50-2.66; 1y: 1.58-3.28), higher medical complexity (aOR range 30d: 2.11-6.23; 1y: 1.96-7.34), multiple substance use disorders (SUD; aOR 30d: 1.81 (95% CI 1.44, 2.27) 1y: 1.48 [95% CI 1.36, 1.62]), and length of hospitalization (aOR 30d: 6.78 [95% CI 4.85, 9.47] 1y: 3.45 [95% CI 2.96, 4.01]) were associated with increased all-cause mortality following hospitalization. Homelessness (aOR 30d: 0.75 [95% CI 0.63, 0.90]; 1y: 0.85 [95 % CI 0.80, 0.91]), depression (aOR 1y: 0.89 [95 % CI 0.84, 0.95]), bipolar disorder (aOR 1y: 0.88 [95% CI 0.82, 0.94]), buprenorphine receipt (aOR 1y: 0.79 [95% CI 0.69, 0.91]), and service connection (aOR 30d: 0.76 [95% CI 0.60, 0.97] 1y: 0.64 [95 % CI 0.59, 0.70]) were associated with reduced all-cause mortality. Younger age (aOR range 30d: 3.21-5.24; 1y: 2.71-2.38), homelessness (aOR 1y: 1.40 [95% CI 1.20, 1.63]), and multiple SUD (aOR 1y: 1.78 [95% CI 1.33, 2.38]) were among factors associated with increased opioid-related mortality after hospitalization. Black race (aOR 1y: 0.61 [95% CI 0.50, 0.74]) and higher service connection (aOR 30d: 0.41 [95 % CI 0.21, 0.81]; 1y: 0.53 [95% CI 0.43-0.66]) were associated with reduced opioid-related mortality after hospitalization.

Conclusions: Several patient-level factors were associated with increased all-cause mortality (e.g., length of hospital stay), reduced all-cause mortality (e.g., homelessness), increased opioid-related mortality (e.g., multiple SUD), and reduced opioid-related mortality (e.g., service connection) after hospitalization. This information provides a roadmap for future development and study of tailored supports and risk stratification tools to enhance post-hospitalization transitional care for patients with OUD.

Related protocols: CTN-0087

Abstract:

In this study, researchers sought to identify the sociodemographic and clinical characteristics associated with homelessness, and explore the relationship between homelessness and treatment outcomes among Black individuals. The study was 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.

Black participants were mostly unmarried and male, and about a third were aged 21–30 years. Among people experiencing homelessness, 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 homelessness 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 homelessness with additional clinical supports such as those provided by a clinical trial.

Related protocols: CTN-0051

Abstract:

Objective: Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients’ demographic and clinical characteristics were associated with better response to one medication or the other.

Methods: In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder (CTN-0051), 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing.

Results: In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal).

Conclusions: Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

Related protocols: CTN-0051

Abstract:

A recent study found that homeless individuals with opioid use disorder (OUD) had a lower risk of relapse on extended-release naltrexone (XR-NTX) versus buprenorphine-naloxone, whereas non-homeless individuals had a lower risk of relapse on BUP-NX. This secondary analysis of data from CTN-0051 (X:BOT) examined differences in mediation pathways to medication effect between homeless and non-homeless participants. The X:BOT trial was an open-label randomized controlled, 24-week comparative effectiveness trial held in 8 community addiction treatment programs in the U.S. Participants were English-speaking adults with DSM-5 OUD, recruited during inpatient admission (N=570) and then randomized to monthly injection of XR-NTX or daily sublingual BUP-NX.

In this secondary analysis, mediation analysis estimated the direct effect of XR-NTX versus BUP-NX on relapse and indirect effect through mediators of medication adherence, use of illicit opioids, depressive symptoms, and pain, separately by homeless status.

For the homeless subgroup, analysis found that the protective indirect path contributed a 3.4 percentage point reduced risk of relapse comparing XR-NTX to BUP-NX (explaining 21% of the total effect). For the non-homeless subgroup, the indirect path contributed a 9.4 percentage point increased risk of relapse comparing XR-NTX to BUP-NX (explaining 57% of the total effect).

Conclusions: A novel approach to medication analysis shows that much of the difference in medication effectiveness (XR-NTX versus BUP-NX) on opioid relapse among non-homeless adults with opioid use disorder appears to be explained by mediators of adherence, illicit opioid use, depressive symptoms, and pain.

Related protocols: CTN-0051

Abstract:

Although HIV risk behaviors such as substance use and condomless sex are prevalent among people currently seeking or receiving services at substance use disorder (SUD) treatment programs, associations with housing status in this population have not been well studied. This study examined the associations between housing status, substance use, and HIV-related sexual risk behaviors among 1281 participants from 12 U.S. community-based SUD programs. In addition, substance use was examined as a potential mediator of the relationship between housing status and sexual risk behaviors.

Researchers conducted Chi-square, univariate, and multivariate logistic regression models on data from the NIDA Clinical Trials Network HIV Rapid Testing and Counseling study (CTN-0032). Path analysis was used to test the mediation and indirect effects.

Unstable housing was significantly associated with having multiple concurrent condomless sex partners, condomless sex with non-primary partners, and partners of unknown HIV serostatus. Homelessness was significantly associated with condomless vaginal sex and condomless sex with any substance use. The path between unstable housing and sexual risk behaviors was mediated by problematic drug use, particularly by cocaine, opioids, and marijuana use.

Conclusions: Because housing status impacts HIV risk behaviors for individuals in SUD treatment programs, both housing status and substance use behaviors should be assessed upon program entry in order to identify and mitigate risk behaviors.

Related protocols: CTN-0032

Abstract:

The growing use of newer communication and internet technologies, even among low income and transient populations, require research staff to update their outreach strategies to ensure high follow-up and participant retention rates. This paper presents the views of research assistants on the use of cell phones and the internet to track participants in a multi-site randomized trial of substance use disorder treatment. Pre-interview questionnaires exploring tracking and other study-related activities were collected from 21 research staff across the 10 sites participating in the National Drug Abuse Treatment Clinical Trials Network study CTN-0044, about an online intervention for substance use disorders (Therapeutic Education System). Data were then used to construct a semi-structured interview guide which, in turn, was used to interview 12 of the same staff members. The questionnaires and interview data were entered in Atlas.ti and analyzed for emergent themes related to the use of technology for participant tracking purposes.

Study staff reported that most participants had cell phones, despite having unstable physical addresses and landlines. The incoming call feature of most cell phones was useful for participants and research staff alike, and texting proved to have additional benefits. However, reliance on participants’ cell phones also proved problematic at times. Even homeless participants were found to have access to the internet through public libraries and could respond to study staff e-mails. Some study sites opened generic social media accounts, through which study staff sent private messages to participants. However, the Institutional Review Board (IRB) approval process for tracking participants using social media at some sites was prohibitively lengthy. Internet searches through Google, national paid databases, obituaries, and judiciary websites were also helpful tool.

Conclusions: Research staff perceive that cell phones, internet searches, and social networking sites were effective tools to achieve high follow-up rates in drug abuse research and should be used in addition to established study procedures. Studies should incorporate cell phone, texting, and social network website information on locator forms; obtain IRB approval for contacting participants using social networking websites; and include web searches, texting, and the use of social media in staff training as standard operating procedures.

Related protocols: CTN-0044