Clinical trial NCT05594121: Monthly Versus Daily Buprenorphine Formulations for Treatment of Opiate Use Disorder
Official title: A Pragmatic, Multi-centre, Open-label, Randomized, 12-month, Parallel Group, Superiority Study to Compare the Effectiveness of Subcutaneous Buprenorphine Depot (Sublocade®) vs Daily Sublingual Buprenorphine With Naloxone (Suboxone®) for the Treatment of Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Moderate to Severe Opioid Use Disorder
Lead sponsor: Royal Victoria Hospital, Canada
Sponsor class: OTHER
First posted: 2022-10-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, multi-centre, randomised, controlled, open-label, superiority study with two parallel groups and primary endpoints of opioid positivity and healthcare utilization at 12 months after enrollment. Randomization will be performed with a 1:1 allocation ratio using a stratified, permuted-block group schema according to the following strata (no fixed ratio):

1. RAAM clinic site (Barrie, Orillia, Midland, Wasaga Beach)
2. Severity of OUD according to DSM-V criteria (moderate vs severe)
Primary purpose: TREATMENT

Brief summary: Opioid use disorder and opioid-related deaths are increasing across Canada. The mainstay of medical treatment includes either full (methadone) or partial (buprenorphine) opioid agonist therapy. In Canada, there are 2 buprenorphine formulations, an immediate-release (Suboxone) and extended-release(Sublocade). These treatments have been shown to be equivalent for medication adherence and treatment retention. However, Sublocade costs 8-times more, and 50% of patients must pay out-of-pocket if they prefer this treatment option. This study is needed to demonstrate the superior benefits of Sublocade on important clinical outcomes to demonstrate its cost-effectiveness and justify expanded insured access across Canada.

Detailed description: Opioid use disorder (OUD) is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) as a "problematic pattern of opioid use leading to clinically significant impairment or distress." The DSM-V also uses the number of criteria present to categorize the severity of OUD, with mild OUD defined as having 2-3 criteria present, moderate OUD defined as having 4-5 criteria present, and severe OUD defined as having ≥6 criteria present. Opioid use disorder and opioid-related deaths are increasing in Ontario and Canada. Compared to 2016, the age-adjusted opioid-related mortality rates in 2020 have increased by 161% in Ontario to 16.5 per 100 000 population and 114% in Canada to 16.7 per 100 000 population. Like deaths, opioid-related healthcare utilization as measured by hospitalization and emergency department visits have also been increasing over the same time period. Compared to 2016, the age-adjusted opioid-related hospitalization rates in 2020 have increased by 19.8% in Ontario to 16.3 per 100 000 population and 5.9% in Canada to 17.8 per 100 000 population. Emergency room visits have increased by 166% during the same time period in Ontario to 84.5 per 100 000 population. The median length of hospitalization from 2016 to 2020 has remained unchanged at 3 days (Range 1 to 207 days), with an average cost per hospitalization of $9 626 (CDN) (Range $26 to $296 831). Opiate substitution treatment with either full (methadone) or partial (buprenorphine) opioid agonist therapy (OAT) has been shown to reduce self-reported opioid use or opiate positive urine drug tests compared to detoxification or psychological treatments. There are 2 main opioid agonists used to treat OUD, methadone and buprenorphine. Buprenorphine has been approved by Health Canada for use in OUD, and is available in immediate (Suboxone®) and extended-release (Sublocade®) formulations. Monthly subcutaneous buprenorphine (SC-BPN-XR) has been shown to be non-inferior to daily sublingual buprenorphine/naloxone (SL-BPN/NX) for medication adherence and treatment retention. The Canadian pharmaceutical costs of Sublocade® and Suboxone® differ substantially , with monthly costs for Sublocade 8-fold higher than Suboxone. The majority of patients meeting criteria for Sublocade® use must pay for the drug out-of-pocket resulting in significant restriction to access for this population that has a high burden of chronic homelessness and poverty. A recent pharmacoeconomic report by the Canadian Agency for Drugs and Technologies in Health (CADTH) concluded that the current evidence base for supporting cost-effectiveness of Sublocade® over Suboxone is limited by the absence of studies directly comparing the effectiveness of the two treatments on clinically important outcomes such as healthcare utilization. With limited evidence and significant uncertainty, the CADTH analysis suggested that a price reduction of at least 73% would be required for Sublocade® to be a cost-effective alternative to Suboxone. A real-world (pragmatic) randomised study is therefore needed to compare the treatment effectiveness of Sublocade® versus Suboxone® in Canadian patients attending RAAM clinics for OAT for moderate- to severe-OUD. This study is needed to demonstrate the superior benefits of Sublocade® on important clinical outcomes such as reduced opioid and healthcare utilization in order to demonstrate its cost-effectiveness and justify expanded access for this at-risk population.

Eligibility criteria: Inclusion Criteria:

* Ages 18 to 65 years old
* OAT indicated for moderate- to severe-OUD
* Attend a RAAM clinic in the North Simcoe Muskoka Local Health Integrated Network for opiate substitution treatment
* Successfully completed induction and stabilization OAT with Suboxone® tablet or film defined as receiving 8mg/2mg to 24mg/6mg of Suboxone® for ≥7 days with no evidence of allergic reaction to Suboxone®, Clinical Opiate Withdrawal Scale (COWS) score ≤12 (scale:0-48) for ≥24 hours, and Opiate Craving Visual Analog Scale (VAS) score ≤20 (scale:0-100)) for ≥24 hours
* Must have an active Ontario Health Insurance Plan number
* Must have a telephone that can receive calls, text messages or emails
* Must have drug insurance coverage for either medication for duration of study or demonstrate ability to pay for the drug out-of-pocket

Exclusion Criteria:

* Receiving any investigational drug for OUD in previous 4 weeks
* Congenital long QTc syndrome or QTc prolongation at baseline by electrocardiogram (QTc ≥450 milliseconds in men and QTc ≥470 milliseconds in women)
* Pregnant or lactating women
* Women of childbearing potential who are not using an effective and reliable method of contraception

Primary outcomes:
measure: Opioid positivity
timeFrame: every 7 days for 12 months
measure: Healthcare utilization
timeFrame: 12 months
Secondary outcomes:
measure: Medication Satisfaction
timeFrame: Every 6 weeks starting on week 6 after randomization for 12 months
measure: Quality of Life Score
timeFrame: At time of randomization (baseline), then week 12, week 24 and week 36
measure: Clinic Retention
timeFrame: 12 months
measure: Mortality
timeFrame: 12 months
Other outcomes:
Locations:
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Barrie
country: Canada
facility: RAAM Clinic (Barrie)
state: Ontario
city: Midland
country: Canada
facility: RAAM Clinic (Midland0
state: Ontario
city: Orillia
country: Canada
facility: RAAM Clinic (Orillia)
state: Ontario
city: Wasaga Beach
country: Canada
facility: RAAM Clinic (Wasaga Beach)
state: Ontario
Study officials:
affiliation: Royal Victoria Regional Health Centre
name: Philip Wong, MN
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Victoria Regional Health Centre
name: Giulio DiDiodato, PhD
role: PRINCIPAL_INVESTIGATOR
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