Monthly Versus Daily Buprenorphine Formulations for Treatment of Opiate Use Disorder

NCT ID: NCT05594121

Last Updated: 2022-10-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-31
• Study Completion Date: 2024-12-31

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.

Conditions

Moderate to Severe Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Extended-release subcutaneous buprenorphine (SC-BPN-XR)

For eligible patients randomly allocated to SC-BPN-XR, the first dose will be administered at the time of randomization (Day 0). SC-BPN-XR comes in two formulations, 100 mg and 300 mg buprenorphine doses in a pre-filled syringe. SC-BPN-XR administration is by subcutaneous injection in the abdomen. SC-BPN-XR is administered at intervals ≥26 days. For patients randomly allocated to SC-BPN-XR, they will receive the 300 mg dose for the first 2 months, followed by the 100 mg dose every month until the end of the 12-month period. All SC-BPN-XR doses will be administered in clinics by trained personnel. All patients receiving SC-BPN-XR will have their vital signs monitored every 5 minutes for 15 minutes after the injection before leaving the clinic.

Group Type: EXPERIMENTAL

Extended Release Subcutaneous Buprenorphine

Intervention Type: DRUG

Monthly subcutaneous injections of long-acting buprenorphine

Immediate-release sublingual buprenorphine/naloxone (SL-BPN/NX)

For eligible patients randomly allocated to SL-BPN/NX, the first study dose will be administered at the time of randomization (Day 0) and will match the SL-BPN/NX type (tablet versus film), route (sublingual versus buccal) and dose used for stabilization prior to study enrollment. For the first 2 weeks of the study period, all SL-BPN/NX administration will be directly observed at community pharmacies by trained personnel according to the usual standard of care. Subsequent to this period, healthcare providers and participants will develop a care plan for ongoing directly observed therapy vs unsupervised take-home dosing according to usual standard of care.

Group Type: ACTIVE_COMPARATOR

Immediate Release Sublingual Buprenorphine

Intervention Type: DRUG

Daily sublingual fast-acting buprenorphine

Interventions

Extended Release Subcutaneous Buprenorphine

Monthly subcutaneous injections of long-acting buprenorphine

Intervention Type: DRUG

Immediate Release Sublingual Buprenorphine

Daily sublingual fast-acting buprenorphine

Intervention Type: DRUG

Other Intervention Names

Sublocade; Suboxone

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Victoria Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Giulio DiDiodato

Chief Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philip Wong, MN

Role: PRINCIPAL_INVESTIGATOR

Royal Victoria Regional Health Centre

Giulio DiDiodato, PhD

Role: PRINCIPAL_INVESTIGATOR

Royal Victoria Regional Health Centre

Locations

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

RAAM Clinic (Barrie)

Barrie, Ontario, Canada

RAAM Clinic (Midland0

Midland, Ontario, Canada

RAAM Clinic (Orillia)

Orillia, Ontario, Canada

RAAM Clinic (Wasaga Beach)

Wasaga Beach, Ontario, Canada

Countries

Canada

Central Contacts

Kelly Cruise, BHSc

Role: CONTACT

cruisek@rvh.on.ca

7057289090 ext. 45639

Christine DiMarco

Role: CONTACT

dimarcoc@rvh.on.ca

7057289090 ext. 43341

Facility Contacts

Kelly Cruise, BHSc

Role: primary

cruisek@rvh.on.ca

7057289090 ext. 45639

Giulio DiDiodato, PhD

Role: backup

didiodatog@rvh.on.ca

7057289090 ext. 45641

Brian Irving, RCS

Role: primary

irvingb@rvh.on.ca

7057289090 ext. 24311

Philip Wong, MN

Role: backup

wongp@rvh.on.ca

7057289090 ext. 24327

Brian Irving, RCS

Role: primary

irvingb@rvh.on.ca

7057289090 ext. 24311

Brian Irving, RCS

Role: primary

irvingb@rvh.on.ca

7057289090 ext. 24311

Brian Irving, RCS

Role: primary

irvingb@rvh.on.ca

7057289090 ext. 24311

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R22-004

Identifier Type: -

Identifier Source: org_study_id