Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) (SALOME)

• ClinicalTrials.gov Identifier: NCT01447212
• Recruitment Status: Completed
• First Posted: October 6, 2011
• Last Update Posted: June 7, 2016
• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR); Providence Healthcare; Innerchange Charitable Society
• Information provided by (Responsible Party): University of British Columbia

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Opioid Dependence; Heroin Dependence	Drug: Hydromorphone, Injectable; Drug: Diacetylmorphine, injectable; Drug: Hydromorphone, liquid oral; Drug: Diacetylmorphine, liquid oral	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 202 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2011
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: February 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Hydromorphone; Phase I: Injectable Hydromorphone is received for 6 months of the study. Phase II: At 6 months, participants are randomized to either: 1) stay on injectable hydromorphone; or 2) switch to oral hydromorphone, for another six months.	Drug: Hydromorphone, Injectable; Phase I: 3x daily, up to 500mg per day, for 6 months. Phase II: At 6 months, participants are randomized to either: 1) stay on injectable hydromorphone; 2) switch to oral hydromorphone, for another 6 months.; Drug: Hydromorphone, liquid oral; Study Phase II: After 6 months of receiving Hydromorphone injectable , participants will be randomized to stay on injectable hydromorphone or switch to oral hydromorphone, for another six months. Oral = experimental; injectable = active comparator
Active Comparator: Diacetylmorphine; Phase I: Injectable Diacetylmorphine is received for 6 months of the study. Phase II: At 6 months, participants are randomized to either: 1) stay on injectable Diacetylmorphine; or 2) switch to oral Diacetylmorphine, for another six months.	Drug: Diacetylmorphine, injectable; Phase I: 3x daily, up to 1,000mg per day, for 6 months. Phase II: At 6 months, participants are randomized to either: 1) stay on injectable diacetylmorphine; 2) switch to oral diacetylmorphine, for another 6 months.; Drug: Diacetylmorphine, liquid oral; Study Phase II: After 6 months of receiving Diacetylmorphine injectable, participants will be randomized to stay on injectable Diacetylmorphine or switch to oral Diacetylmorphine, for another six months. Oral = experimental; injectable = active comparator

Outcome Measures

Primary Outcome Measures :

1. Change in days of illicit heroin use from baseline. [ Time Frame: baseline and 6 months ]
   Use of illicit heroin at a time point is defined as the number of days of illicit ("street") heroin in the prior 30 days of the 6 month treatment period by means of self report.

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Canada, British Columbia

SALOME Research Office

Vancouver, British Columbia, Canada, V6B 1C8

Sponsors and Collaborators

University of British Columbia

Canadian Institutes of Health Research (CIHR)

Providence Healthcare

Innerchange Charitable Society

Investigators

• Principal Investigator: Eugenia Oveido-Joekes, Ph.D.; University of British Columbia
• Principal Investigator: Michael R Krausz, M.D.; University of British Columbia

More Information

Additional Information:

SALOME webpage. 

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: University of British Columbia
• ClinicalTrials.gov Identifier: NCT01447212
• Other Study ID Numbers: H09-01455
• First Posted: October 6, 2011
• Last Update Posted: June 7, 2016
• Last Verified: June 2016

Keywords provided by University of British Columbia:

Opioid Dependence; Long-term Opioid Injectors; Opioid Substitution Treatment; Hydromorphone; Diamorphine; Diacetylmorphine

Additional relevant MeSH terms:

Opioid-Related Disorders; Heroin Dependence; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Hydromorphone; Heroin; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents