Scott Harrison

Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence: A Randomized Clinical Trial

IMPORTANCE Diacetylmorphine hydrochloride (the active ingredient in heroin), delivered under supervision, is effective for the treatment of severe opioid use disorder. However, owing to political and regulatory barriers, it is not available in many settings around the world, which limits the options for many long-term street opioid injectors not attracted into or retained in available treatments. OBJECTIVE To test if injectable hydromorphone hydrochloride is noninferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention. DESIGN, SETTING, AND PARTICIPANTS The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized 202 long-term street opioid injectors in Vancouver, British Columbia, Canada. Eligible participants were recruited between December 19, 2011, and December 18, 2013. Both intent-to-treat (ITT) and per-protocol (PP) analyses were conducted. INTERVENTIONS Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision. MAIN OUTCOMES AND MEASURES Primary and coprimary efficacy outcomes were self-reported days of street heroin use (primary), days of any street-acquired opioids in the prior 30 days (noninferiority margin, 4 days), and the proportion of urinalyses positive for street heroin markers (margin, 10% of the observed rate in the diacetylmorphine group). The mean differences between diacetylmorphine and hydromorphone for the ITT and PP analyses were reported. RESULTS The study included 202 participants; 100 randomized to receive hydromorphone and 102 to diacetylmorphine. Their mean (SD) age was 44.33 (9.63) years, and 30.7% (62 of 202) were women. Noninferiority of hydromorphone was confirmed in the PP analysis (-1.44; 90% CI, -3.22 to 0.27) for street heroin use, although the margin of 4 days was not excluded in the ITT analysis (-2.34; 90% CI, -4.14 to -0.52). Noninferiority was confirmed for any street opioids in the ITT analysis (-0.85; 90% CI, -2.97 to 1.25) and the PP analysis (-0.15; 90% CI, -2.09 to 1.76), as well as for the urinalyses (0.09; 90% CI, -0.02 to 0.19 for the ITT analysis and 0.13; 90% CI, 0.02-0.24 for the PP analysis). There were 29 SAEs considered to have some relationship with the injection medication, 5 in the hydromorphone group and 24 in the diacetylmorphine group (rate ratio, 0.21; 95% CI, 0.06-0.69). Seizures and overdoses accounted for 25 of the 29 related SAEs. CONCLUSIONS AND RELEVANCE This study provides evidence to suggest noninferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence. In jurisdictions where diacetylmorphine is currently not available or for patients in whom it is contraindicated or unsuccessful, hydromorphone could be offered as an alternative. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01447212.

The Role of Gender in Factors Associated With Addiction Treatment Satisfaction Among Long-Term Opioid Users

Objectives:To identify factors associated with Opioid Agonist Treatment (OAT) satisfaction and to determine whether these relationships are gender specific. Methods:This study was based on data collected in a cross-sectional study among long-term opioid-dependent individuals (n = 160; 46.3% women). Participants completed the Client Satisfaction Questionnaire in reference to OAT episodes. Sociodemographic, illicit substance use, health, and addiction treatment history data were collected. Multivariable linear regression was used to determine the relationship between these variables and treatment satisfaction. To explore the potential role of gender in these identified relationships stratified multivariable models were tested. Additional open-ended questions regarding positive and negative perceptions of treatment were collected, and a thematic analysis was conducted. Results:In the multivariable linear regression model, participants who were older, of Aboriginal ancestry, and currently receiving OAT had higher OAT satisfaction scores, whereas participants who had methadone dose preferences of 30 mg or less had lower OAT satisfaction. In stratified analyses among women, the relationship between preferred methadone dose and current OAT remained significantly associated with satisfaction. Open-ended positive and negative perceptions complemented and provided further valuable data to interpret these identified relationships. Conclusions:To our knowledge, this is the first study to explore the potential role of gender in factors associated with OAT satisfaction. These findings provide valuable information to health care providers working in OAT settings regarding how to address women and mens OAT needs and improve treatment satisfaction.

Willingness to access an in-hospital supervised injection facility among hospitalized people who use illicit drugs

BACKGROUND Despite the reliance on abstinence-based drug policies within hospital settings, illicit drug use is common among hospitalized patients with severe drug addiction. Hospitalized patients who use illicit drugs (PWUDs) have been known to resort to high-risk behavior to conceal their drug use from healthcare providers. Novel interventions with the potential to reduce high-risk behavior among PWUDs in hospital settings have not been well studied. OBJECTIVE The objective of the study was to examine factors associated with willingness to access an in-hospital supervised injection facility (SIF). DESIGN Data were derived from participants enrolled in 2 Canadian prospective cohort studies involving PWUDs between June 2013 and November 2013. A cross-sectional study surveying various sociodemographic characteristics, drug use patterns, and experiences was conducted. SETTING Vancouver, Canada. MEASUREMENTS Bivariable and multivariable logistic regression analyses were used to explore factors significantly associated with willingness to access an in-hospital SIF. RESULTS Among 732 participants, 499 (68.2%) would be willing to access an in-hospital SIF. In multivariable analyses, factors positively and significantly associated with willingness to access an in-hospital SIF included: daily heroin injection (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.20-3.11); having used illicit drugs in hospital (AOR = 1.63; 95% CI: 1.18-2.26); and having recently used an SIF (AOR = 1.53; 95% CI: 1.10-2.15). CONCLUSIONS Our findings highlight the potential of in-hospital SIFs to complement existing harm reduction programs that serve PWUD. Moreover, an in-hospital SIF may minimize the harms associated with high-risk illicit drug use in the hospital.

The Role of Gender in Suicidal Ideation among Long-term Opioid Users

Objective: This study aims to examine factors associated with suicidal ideation among people with opioid dependence and to explore whether these factors are gender-specific. Methods: Cross-sectional data were collected among long-term opioid-dependent individuals (n = 176; 46.0% women). Lifetime histories of suicidal ideation were measured using the Composite International Diagnostic Interview, and additional data were collected regarding sociodemographic characteristics, drug use, health, and adverse life events. Multivariable logistic regression was used to determine the relationships between these variables and suicidal ideation for the full study sample and separately for women and men to explore the potential role of gender. Results: A total of 43.8% (n = 77) of participants reported a lifetime history of suicidal ideation. Among those with suicidal ideation, 49.3% were women and the overall average age of first ideation was 19.82 years (SD, 11.66 years). Results from multivariable analyses showed that a history of depression, anxiety, and childhood emotional neglect and the number of lifetime traumatic events were significantly associated with higher odds of suicidal ideation. The gender-based analysis suggested that histories of depression and anxiety remained independently associated with lifetime suicidal ideation among women, whereas for men, childhood emotional neglect and the number of lifetime potentially traumatic events were independently associated with lifetime suicidal ideation. Conclusions: This study offers a critical first step to understanding factors associated with suicidal ideation among long-term opioid-dependent men and women and the potential importance of gender-sensitive approaches for suicidal behavior interventions. These data inform further research and clinical opportunities aiming to better respond to the psychological health needs of this population.

Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder

AIMS To review the safety profile of injectable hydromorphone and diacetylmorphine and explore if adverse events (AEs) or serious adverse events (SAEs) were associated with dose and patterns of attendance. METHODS This was a non-inferiority randomized double-blind controlled trial (Vancouver, Canada) testing hydromorphone (n=100) and diacetylmorphine (n=102) for the treatment of severe opioid use disorder. Medications were delivered under the supervision of trained Registered Nurses up to three times daily. AEs were described using MedDRA codes. RESULTS Most common related AEs included immediate post-injection reaction or injection site pruritus reactions, somnolence and opioid overdoses. Adjusted analysis indicated that participants in the hydromorphone group were less likely to have any related AE or SAE compared to the diacetylmorphine group. Related somnolence and opioid overdose events were distributed throughout the six months treatment period. In the diacetylmorphine group, five of the eleven related SAE opioid overdoses (requiring naloxone) occurred in the first 30days since most recent treatment initiation. Analysis of somnolence and opioid overdose (AEs and SAEs) event rates by received dose suggested a non-linear relationship. However, in the diacetylmorphine group higher event rates per person days were recorded at lower doses. CONCLUSIONS When injectable hydromorphone and diacetylmorphine are individually dosed and monitored, their opioid-related side effects, including potential fatal overdoses, are safely mitigated and treated by health care providers. In the midst of an opioid overdose epidemic, injectable options are timely to reach a very important minority of people who inject street opioids and are not attracted to other treatments.

Predictors of treatment allocation guesses in a randomized controlled trial testing double-blind injectable hydromorphone and diacetylmorphine for severe opioid use disorder

Abstract Background: SALOME (Study to Assess Longer-term Opioid Medication Effectiveness) tested in a double-blind non-inferiority clinical trial if hydromorphone could be as effective as diacetylmorphine for severe opioid use disorder. Although participants did not guess treatment correctly beyond what is expected by chance, perceived treatment assignment could affect patients’ response to treatment. This study tested if treatment allocation guess is associated with treatment outcomes and identified predictors of guess. Methods: Data were obtained through questionnaires and clinical records. Participants were asked what medication they thought they were receiving (diacetylmorphine, hydromorphone or unsure) and their open-ended reasons. Multinomial logistic regression was used to assess the predictors of treatment guess. An inductive thematic analysis was used to code open-ended responses. This clinical trial was registered with U.S. National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT01447212). Findings: Participants referred to prior experiences with opioids and the presence or absence of specific drug effects as reasons for their guesses. There were no differences in illicit opioid use and retention by guess; however those who guessed diacetylmorphine had better physical and mental health scores. Participants with a treatment-related observed drowsiness event, and higher perceived drug-related high scores were more likely to guess diacetylmorphine compared to hydromorphone. Guessing hydromorphone was more likely among those who made negative comments as reasons for treatment guesses. Conclusions: Understanding the clues participants use for treatment allocation guesses and relating them to treatment expectations could be integrated with accurate information about the treatment, providing an opportunity for patient–physician shared decision-making in opioid maintenance treatment. Clinical trial registration: U.S. National Institutes of Health; ClinicalTrials.gov Identifier: NCT01447212; https://clinicaltrials.gov/ct2/show/NCT01447212

Characteristics and response to treatment among Indigenous people receiving injectable diacetylmorphine or hydromorphone in a randomised controlled trial for the treatment of long‐term opioid dependence

INTRODUCTION AND AIMS To determine the effectiveness of injectable hydromorphone and dicaetylmorphine for Indigenous participants in the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) clinical trial. The study additionally aims to explore the prevalence and frequency of crack cocaine use among subgroups of participants (by gender and ethnicity). This secondary analysis is particularly relevant given the current need for expanded medication assisted treatments for opioid dependence across North America. DESIGN AND METHODS Participants self-identifying as First Nations, Métis or Inuit were included in the analysis of Indigenous participants. Six-month treatment outcomes are reported as the difference between diacetylmorphine and hydromorphone treatment arms among Indigenous participants and change from baseline to 6 months in each treatment arm. Differences in outcomes are tested between Indigenous and non-Indigenous participants. Crack cocaine use was explored to determine differences between and within subgroups. RESULTS Approximately one-third of SALOME participants self-identified as Indigenous. Indigenous participants presented to treatment with more structural vulnerabilities (e.g. lower education, higher rates of foster care and separation from biological parents) compared to non-Indigenous participants. After 6 months, Indigenous participants in both treatment arms had a significant reduction in days of street heroin use, opioid use, crack cocaine use and illegal activity. Treatment retention did not differ by treatment arm. DISCUSSION AND CONCLUSIONS Indigenous people that are not engaged by first-line treatments for opioid dependence are in need of effective alternative treatments. Given the political and logistical barriers facing diacetylmorphine, hydromorphone could serve as a more accessible medication to reach and treat this population. [Oviedo-Joekes E, Palis H, Guh D, Marchand K, Brissette S, Lock K, MacDonald S, Harrison S, Anis AH, Krausz M, March DC, Schechter MT. Characteristics and response to treatment among Indigenous people receiving injectable diacetylmorphine or hydromorphone in a randomised controlled trial for the treatment of long-termopioid dependence. Drug Alcohol Rev 2018;37:137-146].