Clinical trial NCT01447212: Study to Assess Longer-term Opioid Medication Effectiveness (SALOME)
Official title: SALOME: Multi-Centre, Double Blind Randomized Controlled Trial Comparing The Effectiveness Of Diacetylmorphine Vs. Hydromorphone For The Treatment Of Long-Term Injection Opioid Users Who Do Not Benefit From Available Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid Dependence
Heroin Dependence
Keywords: Opioid Dependence
Long-term Opioid Injectors
Opioid Substitution Treatment
Hydromorphone
Diamorphine
Diacetylmorphine
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Providence Healthcare
name: Innerchange Charitable Society
First posted: 2011-10-06
Enrollment: 202
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study, SALOME, is to determine if 1) the closely supervised provision of injectable, hydromorphone (HDM; trade name Dilaudid™) is as effective as injectable diacetylmorphine (DAM; heroin) in the treatment of chronic, multi-morbid opioid-dependent individuals who have not benefited sufficiently from conventional treatments, and if a switch to the oral equivalent of hydromorphone and diacetylmorphine is as effective as the injection form. The availability of an effective, licensed opioid medication such as hydromorphone, for substitution treatment of chronic, multi-morbid treatment-refractory opioid-dependent individuals, would be of immense impact locally and internationally. It could help to establish alternative treatment options where for non-medical reasons Heroin Assisted Treatment would not be acceptable. Thus, one result could be the expansion of treatment options for the most difficult to treat heroin dependent persons. This would also be an important step for secondary prevention of HIV and Hepatitis C as well as a better integration of those patients in other medical treatments. Switching from intravenous to oral application would also reduce a lot of potential risk factors (like overdose, seizures, infections, etc) and side effects associated with the injection route. Additionally it could make these treatments more feasible in normal treatment settings, like existing methadone services.

Detailed description: SALOME is two-stage single centre (Vancouver) phase III, randomized, double blind controlled trial involving a total of 202 individuals with chronic opioid-dependence who are not benefiting currently from conventional therapies.

Objectives:

The general objectives of this study are to determine whether 1) the closely supervised provision of injectable, hydromorphone is as effective as injectable diacetylmorphine in recruiting, retaining, and benefiting chronic, multi-morbid opioid-dependent individuals who have not benefited sufficient from conventional treatments, and 2) if the switch to the oral equivalent of hydromorphone and diacetylmorphine after six-months is as effective as the injection form.

Secondary outcomes will be evaluated looking at the benefits for the drug users and society of each form of treatment including health status, treatment retention, use of additional methadone, cocaine use and criminal involvement.

Randomization and Treatment Arms:

Stage I: Half of the 202 participants will be randomized to receive injectable diacetylmorphine, and the other half will receive injectable hydromorphone. Stage I will involve 6-months of treatment and the primary outcome will be change in illicit heroin use in the prior 30 days at 6 months.

Stage II: All volunteers retained in injection treatment at the end of Stage I will be eligible to enter Stage II Half the participants will then be randomized to continue injection treatment exactly as in Stage I on a blinded basis while the other half will switch to the oral equivalent of the same medication (diacetylmorphine or hydromorphone). Stage II will involve 6-months of treatment and the primary outcome will be illicit heroin use in the prior 30 days at 6 months after randomization into Stage II.

Individuals completing Stage I will be eligible for Stage II provided they are still receiving injection medication at the treatment clinic. Participants will be excluded from Stage II if they meet any of the exclusion criteria above which may have changed since entry into Stage I. Patients who switch completely to other treatments or abstinence during Stage I will not be randomized to Stage II.

Given that at the present time DAM is not a licensed drug in Canada and HDM for substitution treatment can only be provided as a drug under investigation, at the end of the second study phase patients cannot longer receive these medications. Thus, study treatments will be provided for 12 months followed by a period of up to 1-month during which participants still being treated with DAM or HDM will be tapered and transitioned to conventional therapies such as methadone. From the end of phase two and transitioning period (12 to 13 months) to the next follow-up evaluation (18 month) participants might be receiving Methadone Maintenance Therapy (MMT), engaged in other addiction treatment, abstinent or untreated, using illicit opioids. The 6 and 12-month study visit at which the primary outcome measures will be assessed will be conducted before any tapering or transition began.

Outcomes and follow-up:

Patients will have research assessments performed during the pre-randomization period, at baseline, and at 3, 6, 9, 12, 18 and 24 months following initial randomization The primary outcome measure (POM) for both Stages I and II will be change in illicit heroin use defined as the number of days of illicit ("street") heroin in the prior 30 days of each endpoint (6 months-Stage I, 12 months-Stage II) by means of self report.

Secondary outcome measures will include health status, safety of the study treatments, treatment retention, use of additional methadone, cocaine use, urinalysis, criminal involvement, gender, ethnicity and victimization, health economics and quality of life and an evaluation of the study blinding.

All self-reported outcomes data collection with the study participants will occur in a face-to-face, fully confidential interview setting at the research centre. The interviews will be conducted by trained field research interviewers, who are not part of the clinical treatment team, using standardized instruments. These include: Baseline and follow-up European version of the Addiction Severity Index (EuropASI); EQ-5D (EuroQoL) Opioid Treatment Index (OTI); SCLR-90; WHO Disability Assessment Schedule II (WHO-DAS II); Maudsley Addiction Profile (MAP); Fagerstrom; Health Utilities Index (HUI) as well as Baseline and Follow-up Socio-Demographic questionnaires. The study blinding will be evaluated by a blinding evaluation instrument which follows best practices and current recommendations for evaluating blinding in randomized controlled trials.

Eligibility criteria: General Inclusion Criteria:

* Regular use of opioids for five years
* Injecting opioids in the past year
* Two attempts at treatment including one methadone (or other substitution)
* Must be a legal adult
* Struggling with drug related problems

General Exclusion Criteria:

* Pregnancy upon study entry
* Diagnosis of severe medical or psychiatric conditions contra-indicated for diacetylmorphine or hydromorphone treatment.

Primary outcomes:
measure: Change in days of illicit heroin use from baseline.
timeFrame: baseline and 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: SALOME Research Office
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Eugenia Oveido-Joekes, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Michael R Krausz, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oviedo-Joekes E, Brissette S, Marsh DC, Lauzon P, Guh D, Anis A, Schechter MT. Diacetylmorphine versus methadone for the treatment of opioid addiction. N Engl J Med. 2009 Aug 20;361(8):777-86. doi: 10.1056/NEJMoa0810635.
citation: Oviedo-Joekes E, Guh D, Brissette S, Marsh DC, Nosyk B, Krausz M, Anis A, Schechter MT. Double-blind injectable hydromorphone versus diacetylmorphine for the treatment of opioid dependence: a pilot study. J Subst Abuse Treat. 2010 Jun;38(4):408-11. doi: 10.1016/j.jsat.2010.03.003. Epub 2010 Mar 31.
citation: Palis H, Marchand K, Guh D, Brissette S, Lock K, MacDonald S, Harrison S, Anis AH, Krausz M, Marsh DC, Schechter MT, Oviedo-Joekes E. Men's and women's response to treatment and perceptions of outcomes in a randomized controlled trial of injectable opioid assisted treatment for severe opioid use disorder. Subst Abuse Treat Prev Policy. 2017 May 19;12(1):25. doi: 10.1186/s13011-017-0110-9.
citation: Oviedo-Joekes E, Guh D, Brissette S, Marchand K, MacDonald S, Lock K, Harrison S, Janmohamed A, Anis AH, Krausz M, Marsh DC, Schechter MT. Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):447-55. doi: 10.1001/jamapsychiatry.2016.0109.
citation: Oviedo-Joekes E, Marchand K, Lock K, MacDonald S, Guh D, Schechter MT. The SALOME study: recruitment experiences in a clinical trial offering injectable diacetylmorphine and hydromorphone for opioid dependency. Subst Abuse Treat Prev Policy. 2015 Jan 26;10:3. doi: 10.1186/1747-597X-10-3.