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.
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.
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.
Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision.
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.
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.
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.
clinicaltrials.gov Identifier: NCT01447212.
Background and aims
Previous research has found diacetylmorphine, delivered under supervision, to be cost‐effective in the treatment of severe opioid use disorder, but diacetylmorphine is not ...available in many settings. The Study to Assess Long‐term Opioid Maintenance Effectiveness (SALOME) randomized controlled trial provided evidence that injectable hydromorphone is non‐inferior to diacetylmorphine. The current study aimed to compare the cost‐effectiveness of hydromorphone directly with diacetylmorphine and indirectly with methadone maintenance treatment.
Design
A within‐trial analysis was conducted using the patient level data from the 6‐month, double‐blind, non‐inferiority SALOME trial. A life‐time analysis extrapolated costs and outcomes using a decision analytical cohort model. The model incorporated data from a previous trial to include an indirect comparison to methadone maintenance.
Setting
A supervised clinic in Vancouver, British Columbia, Canada.
Participants
A total of 202 long‐term street opioid injectors who had at least two attempts at treatment, including one with methadone (or other substitution), were randomized to hydromorphone (n = 100) or diacetylmorphine (n = 102).
Measurements
We measured the utilization of drugs, visits to health professionals, hospitalizations, criminal activity, mortality and quality of life. This enabled us to estimate incremental costs, quality‐adjusted life years (QALYs) and cost‐effectiveness ratios from a societal perspective. Sensitivity analyses considered different sources of evidence, assumptions and perspectives.
Findings
The within‐trial analysis found hydromorphone provided similar QALYs to diacetylmorphine 0.377, 95% confidence interval (CI) = 0.361–0.393 versus 0.375, 95% CI = 0.357–0.391, but accumulated marginally greater costs $49 830 ($28 401–73 637) versus $34 320 ($21 780–55 998). The life‐time analysis suggested that both diacetylmorphine and hydromorphone provide more benefits than methadone 8.4 (7.4–9.5) and 8.3 (7.2–9.5) versus 7.4 (6.5–8.3) QALYs at lower cost $1.01 million ($0.6–1.59 million) and $1.02 million ($0.72–1.51 million) versus $1.15 million ($0.71–1.84 million).
Conclusions
In patients with severe opioid use disorder enrolled into the SALOME trial, injectable hydromorphone provided similar outcomes to injectable diacetylmorphine. Modelling outcomes during a patient's life‐time suggested that injectable hydromorphone might provide greater benefit than methadone alone and may be cost‐saving, with drug costs being offset by costs saved from reduced involvement in criminal activity.
Highlights • Injectable hydromorphone and diacetylmorphine were administered under supervision. • Opioid dependent patients injected an individualized dose up to 3 times per day. • Related events ...were mostly histamine reactions, drowsiness and opioid overdoses. • These related adverse events were all expected and resolved in a timely manner. • All serious adverse events were safely mitigated and treated by health care providers.
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