title: Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01447212.
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada2School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Oviedo-Joekes
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Daphne
authors.initials: D
authors.lastname: Guh
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Brissette
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada2School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Marchand
authors.affiliation: Providence Crosstown Clinic, Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: MacDonald
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Kurt
authors.initials: K
authors.lastname: Lock
authors.affiliation: Providence Crosstown Clinic, Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Harrison
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Amin
authors.initials: A
authors.lastname: Janmohamed
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada2School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Aslam H
authors.initials: AH
authors.lastname: Anis
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada5Department of Psychiatry, University of British Columbia, Vancouver, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Krausz
authors.affiliation: Northern Ontario School of Medicine, Sudbury, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Marsh
authors.affiliation: Centre for Health Evaluation and Outcome Sciences, Providence Health Care, St Paul's Hospital, Vancouver, British Columbia, Canada2School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Schechter
mesh_terms: D000328:Adult; D001955:British Columbia; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D003932:Heroin / Q000009:adverse effects / Q000627:therapeutic use*; D006556:Heroin Dependence / Q000534:rehabilitation*; D006801:Humans; D004091:Hydromorphone / Q000009:adverse effects / Q000627:therapeutic use*; D013287:Illicit Drugs; D007275:Injections, Intravenous; D057194:Intention to Treat Analysis; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D018671:Needle-Exchange Programs; D015813:Substance Abuse Detection
chemical_list: D013287:Illicit Drugs; D003932:Heroin; D004091:Hydromorphone