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Moderate to Severe Opioid Use DisorderPhase 4STOPITNCT05594121

Monthly Versus Daily Buprenorphine Formulations for Treatment of Opiate Use Disorder

A Phase 4 study testing Extended Release Subcutaneous Buprenorphine and Immediate Release Sublingual Buprenorphine in people with Moderate to Severe Opioid Use Disorder, run by Royal Victoria Hospital, Canada at 5 sites in Canada.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Moderate to Severe Opioid Use Disorder
What is being tested?
Extended Release Subcutaneous Buprenorphine and Immediate Release Sublingual Buprenorphine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
5 sitesCanada
Study dates
Dec 2022to Dec 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

5 sites in 1 country.

Kelly Cruise, BHSc contact

7057289090 ext. 45639

cruisek@rvh.on.ca

Christine DiMarco contact

7057289090 ext. 43341

dimarcoc@rvh.on.ca

5 sites in 1 country

Canada5 sites

  • Royal Victoria Regional Health Centre

    Barrie, Ontario, L4M6M2

    Kelly Cruise, BHSc, 7057289090 ext. 45639, cruisek@rvh.on.ca

    Giulio DiDiodato, PhD, 7057289090 ext. 45641, didiodatog@rvh.on.ca

  • RAAM Clinic (Barrie)

    Barrie, Ontario, L4N1K4

    Brian Irving, RCS, 7057289090 ext. 24311, irvingb@rvh.on.ca

    Philip Wong, MN, 7057289090 ext. 24327, wongp@rvh.on.ca

  • RAAM Clinic (Midland0

    Midland, Ontario, L4R0B7

    Brian Irving, RCS, 7057289090 ext. 24311, irvingb@rvh.on.ca

  • RAAM Clinic (Orillia)

    Orillia, Ontario, L3V4S8

    Brian Irving, RCS, 7057289090 ext. 24311, irvingb@rvh.on.ca

  • RAAM Clinic (Wasaga Beach)

    Wasaga Beach, Ontario, L9Z0C4

    Brian Irving, RCS, 7057289090 ext. 24311, irvingb@rvh.on.ca

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
Extended Release Subcutaneous Buprenorphine, Immediate Release Sublingual Buprenorphine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Extended Release Subcutaneous BuprenorphineDrug

    Also called Sublocade

    Monthly subcutaneous injections of long-acting buprenorphine

  • Immediate Release Sublingual BuprenorphineDrug

    Also called Suboxone

    Daily sublingual fast-acting buprenorphine

Study groups in NCT05594121
Study groupRoleWhat they receive
Extended-release subcutaneous buprenorphine (SC-BPN-XR)ExperimentalFor 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.
Receives: Drug: Extended Release Subcutaneous Buprenorphine
Immediate-release sublingual buprenorphine/naloxone (SL-BPN/NX)Active comparatorFor 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.
Receives: Drug: Immediate Release Sublingual Buprenorphine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Opioid positivity

    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.

    Measured: every 7 days for 12 months

  2. Healthcare utilization

    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.

    Measured: 12 months

Secondary outcomes (4)

  1. Medication Satisfaction

    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.

    Measured: Every 6 weeks starting on week 6 after randomization for 12 months

  2. Quality of Life Score

    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.

    Measured: At time of randomization (baseline), then week 12, week 24 and week 36

  3. Clinic Retention

    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.

    Measured: 12 months

  4. Mortality

    Difference in mortality proportions, where mortality is defined as any death attributable to opioid use regardless of the intent.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2022
  2. Study startDec 2022 (estimated)
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05594121
Sponsor's protocol ID
R22-004
Acronym
STOPIT
Status last verified
Oct 2022
First submitted
17 Oct 2022
Last updated
26 Oct 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). (American Psychiatric Publishing, Inc., 2013).

  • Ontario Agency for Health Protection and Promotion. Opioid mortality surveillance report: analysis of opioid-related deaths in Ontario July 2017-June 2018. (2019).

  • Special Advisory Committee on the Epidemic of Opioid Overdoses. Opioid and Stimulant-related Harms in Canada. https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/ (2021).

  • Public Health Ontario. Opioid-related Morbidity and Mortality in Ontario. https://www.publichealthontario.ca/en/data-and-analysis/substance-use/interactive-opioid-tool#/trends (2021).

  • Nielsen S, Larance B, Degenhardt L, Gowing L, Kehler C, Lintzeris N. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016 May 9;(5):CD011117. doi: 10.1002/14651858.CD011117.pub2.

    PubMed 27157143

  • Bruneau J, Ahamad K, Goyer ME, Poulin G, Selby P, Fischer B, Wild TC, Wood E; CIHR Canadian Research Initiative in Substance Misuse. Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018 Mar 5;190(9):E247-E257. doi: 10.1503/cmaj.170958. No abstract available.

    PubMed 29507156

  • Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, Ferri M, Pastor-Barriuso R. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.

    PubMed 28446428

  • Bahji A, Cheng B, Gray S, Stuart H. Reduction in mortality risk with opioid agonist therapy: a systematic review and meta-analysis. Acta Psychiatr Scand. 2019 Oct;140(4):313-339. doi: 10.1111/acps.13088.

    PubMed 31419306

  • Galanter M, Femino J, Hunter B, Hauser M. Buprenorphine Treatment for Opioid Use Disorder in Community-Based Settings: Outcome Related to Intensity of Services and Urine Drug Test Results. Am J Addict. 2020 Jul;29(4):271-278. doi: 10.1111/ajad.13001. Epub 2020 Mar 11.

    PubMed 32162434

  • Wiercigroch D, Sheikh H, Hulme J. A rapid access to addiction medicine clinic facilitates treatment of substance use disorder and reduces substance use. Subst Abuse Treat Prev Policy. 2020 Jan 13;15(1):4. doi: 10.1186/s13011-019-0250-1.

    PubMed 31931831

  • Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for management of opioid use disorder. Am J Health Syst Pharm. 2019 Jul 18;76(15):1097-1103. doi: 10.1093/ajhp/zxz105.

    PubMed 31361869

  • Lofwall MR, Walsh SL, Nunes EV, Bailey GL, Sigmon SC, Kampman KM, Frost M, Tiberg F, Linden M, Sheldon B, Oosman S, Peterson S, Chen M, Kim S. Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Intern Med. 2018 Jun 1;178(6):764-773. doi: 10.1001/jamainternmed.2018.1052.

    PubMed 29799968

  • Rosenthal RN, Ling W, Casadonte P, Vocci F, Bailey GL, Kampman K, Patkar A, Chavoustie S, Blasey C, Sigmon S, Beebe KL. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013 Dec;108(12):2141-9. doi: 10.1111/add.12315. Epub 2013 Sep 18.

    PubMed 23919595

  • Rosenthal RN, Lofwall MR, Kim S, Chen M, Beebe KL, Vocci FJ; PRO-814 Study Group. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA. 2016 Jul 19;316(3):282-90. doi: 10.1001/jama.2016.9382.

    PubMed 27434441

  • Ontario Drug Policy Research Network. Ontario Opioid Prescription Tool. https://odprn.ca/ontario-opioid-drug-observatory/ontario-prescription-opioid-tool/ (2018).

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Extended Release Subcutaneous Buprenorphine and Immediate Release Sublingual Buprenorphine in people with Moderate to Severe Opioid Use Disorder, run by Royal Victoria Hospital, Canada at 5 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Kelly Cruise, BHSc (7057289090 ext. 45639, cruisek@rvh.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Opioid positivity (time frame: every 7 days for 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05594121, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022.

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