Monthly Versus Daily Buprenorphine Formulations for Treatment of Opiate Use Disorder (STOPIT)

October 20, 2022 updated by: Giulio DiDiodato, Royal Victoria Hospital, Canada

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Barrie, Ontario, Canada, L4M6M2
        • Royal Victoria Regional Health Centre
        • Contact:
        • Contact:
      • Barrie, Ontario, Canada, L4N1K4
        • RAAM Clinic (Barrie)
        • Contact:
        • Contact:
      • Midland, Ontario, Canada, L4R0B7
        • RAAM Clinic (Midland0
        • Contact:
      • Orillia, Ontario, Canada, L3V4S8
        • RAAM Clinic (Orillia)
        • Contact:
      • Wasaga Beach, Ontario, Canada, L9Z0C4
        • RAAM Clinic (Wasaga Beach)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Extended Release Subcutaneous Buprenorphine
Monthly subcutaneous injections of long-acting buprenorphine
Other Names:
  • Sublocade
Active Comparator: 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.
Drug: Immediate Release Sublingual Buprenorphine
Daily sublingual fast-acting buprenorphine
Other Names:
  • Suboxone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Opioid positivity
Time Frame: every 7 days for 12 months
Difference in proportions of relapse-free weeks (RFWs) at 12-months from the date of randomization, where relapse-free weeks are defined by the cumulative number of weeks alive during the study period in which there was a negative urine drug screen and negative self-report for non-prescribed opioids. The potential number of RFWs for each patient is the cumulative number of weeks that the patient is alive during the 12-month study period, with a maximum of 48 weeks. A week is defined as a consecutive 7-day period starting on the day of the week that randomization occurred.
every 7 days for 12 months
Healthcare utilization
Time Frame: 12 months
Difference in incidence rates of healthcare days at 12-months from the date of randomization, where healthcare days represent the number of days alive and registered for an emergency room visit or admitted to an acute care or mental health facility for opioid-related harms or poisonings. For each group, the incidence rate is calculated by dividing the total number of healthcare days by the total person days exposure over the study period. The potential number of healthcare days for each patient is the number of days alive during the 12-month study period, with the maximum being 365 days. Any day in which a patient is documented to have had an emergency room visit or is admitted to an acute care or mental health facility for any opioid-related harm or poisoning will be counted as a healthcare day. Only those healthcare days in which opioid use was considered to be influential to the ER visit or hospitalization will be included in the final analysis.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Medication Satisfaction
Time Frame: Every 6 weeks starting on week 6 after randomization for 12 months
Difference in the Medication Satisfaction Questionnaire scores. The questionnaire is a single-item, global, patient-completed instrument that has been validated to measure treatment satisfaction, initially in patients receiving antipsychotic treatment for schizophrenia, but subsequently used in trials measuring satisfaction with opiate substitution treatment. The question will be read aloud by the RAAM clinic healthcare providers or study personnel to the patient. The question asks, "Overall, how satisfied are you with your current Suboxone®/Sublocade® medication?". The responses are on a 7-point Likert scale, ranging from 1=extremely dissatisfied to 7=extremely satisfied.
Every 6 weeks starting on week 6 after randomization for 12 months
Quality of Life Score
Time Frame: At time of randomization (baseline), then week 12, week 24 and week 36
Difference in the World Health Organization Quality of Life - BREF scores (WHOQOL-BREF). The 26-item questionnaire is a validated, self-report instrument that assesses 4 domains of quality of life: physical health (7 items), psychological health (6 items), social relationships (3 items) and environment (8 items). There are also 2 items that measure overall quality of life and general health. The questionnaire takes 15-20 minutes to complete. The questionnaire prefaces each item, "Think about your life in the last two weeks..". The responses are on a 5-point Likert scale, ranging from 1=not at all/very dissatisfied/never/very poor to 5=very good/very satisfied/an extreme amount/extremely/completely/always, depending on the item.
At time of randomization (baseline), then week 12, week 24 and week 36
Clinic Retention
Time Frame: 12 months
Difference in proportion of patients who attend ≥80% of scheduled clinic visits, where a clinic visit is defined as a scheduled visit with a RAAM clinic healthcare provider for any reason, including urine drug testing, medication administration, or counselling. The number of clinic visits any patient will be assigned will include those scheduled as part of the trial and any other visits scheduled at the discretion of the RAAM clinic healthcare providers.
12 months
Mortality
Time Frame: 12 months
Difference in mortality proportions, where mortality is defined as any death attributable to opioid use regardless of the intent.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Royal Victoria Hospital, Canada

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Giulio DiDiodato, PhD, Royal Victoria Regional Health Centre
  • Principal Investigator: Philip Wong, MN, Royal Victoria Regional Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 17, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 26, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R22-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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