SALOMÉ
Study to Assess Longer-term Opioid
Medication Effectiveness
Rationale
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NAOMI:
blinding was not broken among those receiving
hydromorphone;
 almost identical treatment effect compared to
diacetylmorphine (not powered).
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Hydromorphone:
licensed drug in North America;
 similar pharmacodynamic profile of that of morphine, similar
pharmacology of that of diacetylmorphine;
 commonly used as the ‘challenge’ drug in behavioral
experiments studying heroin dependence;
 less stigma attached
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Rationale
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Health Canada denied compassionate access for
diacetylmorphine in May 2008:
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In the course of reviewing your request, we determined that
there are other options (i.e., marketed drugs) that we would
consider alternative to diamorphine at this time.
While studies have shown that diacetylmorphine and
hydromorphone produce similar effects, hydromorphone has
never been evaluated as a substitution treatment option for
opioid dependency.
Investigators
Aslam Anis (Health Economics)
 Suzanne Brissette
 Julie Bruneau
 Amin Janmohamed (Study Pharmacist)
 Michael Krausz (Principal Investigator)
 Bohdan Noysk (Health Economics)
 Eugenia Oviedo-Joekes (Principal Investigator)
 Martin Schechter
 Christian Schultz
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General objectives
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1) to evaluate if the closely supervised provision of injectable,
hydromorphone is as effective as injectable diacetylmorphine in
recruiting, retaining, and benefiting long-term opioid-dependent
individuals who are not benefiting sufficiently from available
treatments, and
2) to evaluate if a switch to the oral equivalent of hydromorphone
and diacetylmorphine after six-months is as effective as
remaining on the injectable medication.
Planned sample n=322
Randomization
Injectable DAM
Injectable HDM
Phase I
Double blind
Non-Inferiority of HDM to DAM
6 months evaluation
Treatment effectiveness
Randomization
Double blind
12 months evaluation
Treatment effectiveness
18 months evaluation
Follow-up
+
Oral HDM
Injectable DAM + Injectable HDM
Non-Inferiority of Oral vs.
Injecting
Phase II
Oral DAM
Double blind
Primary Hypotheses:
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Is injectable hydromorphone not inferior to injectable
diacetylmorphine in reducing illicit heroin use in chronic
intravenous opioid users after six months of treatment? (Stage I)
Following at least six-months of treatment with injection opioids,
is a switch to the oral form of the medication not inferior to
continued injection treatment over the following six-months?
(Stage II).
non-inferiority trial
Participants: inclusion criteria
“chronic injection opioid users who did not benefit
previously from the available therapies”
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Opioid Dependence as confirmed by DSM IV diagnostic criteria;
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19 years of age or older;
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At least 5 years of opioid use;
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Injecting opioids regularly in the past year;
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At least two episodes of opioid addiction treatment (methadone
maintenance, detoxification, residential care, etc), including one
or more episodes of substitution treatment;
Poor physical, psychological, mental or psychosocial functioning;
PRIMARY OUTCOME MEASURE

For both Stages I and II will be change in illicit
heroin use from baseline:
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Use of illicit heroin at a time point is defined as the
number of days of illicit (“street”) heroin use in the
prior 30 days by means of self report (EuropASI).
SECONDARY OUTCOME MEASURES
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Health Status including HIV risk behaviours
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Treatment retention
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Methadone use
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Treatment satisfaction
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Alcohol, tobacco and illicit drugs use
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Urinalysis for markers of street heroin use
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Criminal involvement
OTHER EVALUATIONS
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Safety (Adverse events)
Success of the blinding (potential use of
hydromorphone open-label)
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Treatment effectiveness among women
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Treatment effectiveness among Aboriginal people.
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Histories of victimization
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Health economics (cost-effectiveness)
Sample size
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Calculated based on illicit heroin use as the
primary outcome, for a non-inferiority trial:

For stage II, with an expected decline of 20 days from baseline, a
margin of 4 days, a power of 0.955, an expected loss-to-follow-up rate
of 0.05 and a one-sided alpha level of 0.05, requires 274 participants
(137 per group).
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Thus, in order for 274 participants to enter into stage II, we will need
to randomize 322 volunteers into stage I. The latter will yield a Stage
I non-inferiority trial with a margin of 4 days, a one-tailed alpha level
of 0.05, and a power of approximately 0.965.
TREATMENT: DOUBLE-BLIND HYDROMORPHONE AND
DIACETYLMORPHINE, INJECTABLE AND ORAL
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prescribed and self-administered in the study clinic under
supervision.
self-administered by injection or orally up to three times daily
medication dosage will be prescribed in DAM-equivalent mg
patients can at any time switch partially or totally to oral
methadone
study treatments will be provided for 12 months followed by a 1month transition period
primary outcome measures will be assessed before any tapering or
transition began.
each client will be assigned a psychosocial support worker and
will have access to a defined range of primary care services
matched to the prevalent conditions seen in injection drug users.
in keeping with the Health Canada Best Practices documents for
methadone maintenance, all services will be delivered in a
patient-centred fashion.
IF HYDROMORPHONE IS DEMONSTRATED TO BE
NON-INFERIOR TO DIACETYLMORPHINE …
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We will have established that this more widely
acceptable drug can be used to stabilize the most
adversely affected cases of opioid dependency in a
medically prescribed injection program.
Further study will also be required to show that
open-label hydromorphone can also successfully
attract patients into care and retain them.
Current status
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Funding:
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CIHR grant: approved on March 31, 2009.
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Providence Health Care: 4 years funding for the clinical
portion of the study (Crosstown Clinic).
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Fundraising: Innerchange Foundation to match CIHR’s
funding, St. Paul’s Hospital Foundation.
Health Canada:
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Therapeutic Products Directorate: No objection to our
CTA. Dispensing of the medications upon stability and
sterility testing results.
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Office of Controlled Substances: Section 56 Exemption
obtained on June 2011.