Feasibility of Opioid Injectable Treatment

Supervised Injectable Opioid Treatment (SIOT) is an evidence-based treatment for dependent opioid injectors who have not responded to conventional, oral treatment. This project will implement SIOT as an adjunct to standard opioid agonist treatment (OAT) and explore whether benefits observed during injectable treatment are sustained after transfer to standard OAT. (Standard OAT is either methadone or buprenorphine). The 2-year, open-label non-controlled study will be located in an OAT clinic, where both methadone and buprenorphine are currently provided. We will recruit 20-30 long-term injectors of street opioid, prescribe a combination of parenteral hydromorphone and oral OAT, then around 18 months gradually transfer to standard OAT. Participants will self-administer (intravenous or intramuscular) twice-daily parenteral hydromorphone for 24-months under direct observation by nursing staff. Dosage range 50-400 mg/day (maximum 200 mg/dose). This will be followed by transition to oral agonist treatment (OAT) as per standard of care. The study period extends over 27 months (117 weeks). The first phase of treatment is induction, the progressive increase in injected hydromorphone dosage, until the participant indicates they are comfortable on the dose, or until the maximum dose of 200mg bd is reached. The duration of this phase depends on the participants’ response but is anticipated to run for one week. During this phase the daily administered dose of OAT (methadone or buprenorphine) may also be adjusted to ensure there is no withdrawal experienced in the inter dosing interval. All dose changes are made with monitoring of clinical response using pulse oximetry, subjective and objective assessments. The induction schedule will be consistent with the Guidance for Injectable Opioid Agonist Treatment for Opioid Use (British Columbia Centre on Substance Misuse, undated). The specific dose for hydromorphone for each patient will be decided based on the patient’s rate of drug effect and assessment of patients pulse oximetry during a 15-minute post-injection observation. If after any dose during induction saturation falls to <90%, the next dose will be reduced by 25% and titration will continue. At any stage during induction, if participant reports being happy with the dose, no further increments will be implemented until participant requests a higher dose. The second phase of treatment is stabilization (week 2 to week 4 following treatment initiation), with the dose administered twice a day that participant has indicated they were happy with in the first phase (maximum 200 mg/dose). The third phase is maintenance (week 5 to week 78 following treatment initiation), typically with the same dose twice daily that the participant was stabilized on in phase 2 (maximum 200 mg/dose), allowing psychosocial issues to be addressed in regular clinical reviews (30 min review each fortnight administered by a Registered Nurse) until three months post last hydromorphone injection. The fourth phase (weeks 79-104 following treatment initiation) is weaning of injections and progressive increase in oral OAT dose to ensure withdrawal symptoms are controlled. This weaning may last up to 6 months. The final phase of treatment is a period of 3 months on oral OAT, to determine whether any gains made during injectable treatment are sustained once returned to conventional treatment. Administration of oral methadone (or, if chosen by the participant, buprenorphine) is an integral part of this trial, since the long-term objective is to attract and hold in treatment people who have previously not responded to OAT; previous studies have demonstrated that the availability of injectable treatment is enough incentive to convert many “non-responders” to responders.