Evaluating Buprenorphine/Naloxone Microdosing vs. Standard Dosing in Emergency Departments

NCT04893525 | Recruiting Phase 2 DMC

• 1 other identifier: H20-03698
• Study Type: interventional
• Target: 658
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-centre, open-label RCT at four Emergency Departments (EDs) in British Columbia and Alberta. The purpose of the current study is to compare the effectiveness of buprenorphine/naloxone microdosing and standard dosing take-home induction regimens at enabling patients to successfully complete the induction regimen, and at retaining patients on opioid agonist therapy. We will randomize our enrolled patients to receive take-home microdosing or standard dosing packages of buprenorphine/naloxone. For the microdosing arm, patients immediately start taking low doses that increase to effective levels without requiring them to go into withdrawal. We hypothesize that ED patients provided buprenorphine/naloxone microdosing packages will be more likely to successfully complete the induction period compare to patients provided standard dosing packages. We furthermore hypothesize that those provided microdosing will be more likely to be retained in opioid agonist therapy, and will experience lower overdose, mortality, and healthcare utilization subsequent to their ED visit.

Conditions

Opioid-use Disorder

Keywords

Buprenorphine/naloxone; Suboxone; Opioid agonist treatment; Micro-induction; Microdosing

Outcome Measures

Primary Outcomes (1)

• Number of patients who have filled a prescription for buprenorphine/naloxone within two weeks of their ED visit.

  Number of patients who have filled a prescription for buprenorphine/naloxone within two weeks of their ED visit.

  14 days

Secondary Outcomes (2)

• Number of patients retained in Opioid agonist therapy (OAT) following the ED visit

  30, 90, and 365 days

• Number of fatal or non-fatal overdose events, mortality, ED visits, physician visits, admissions, and days admitted to hospital for patients following ED visit.

  30, 90, and 365 days.

Study Arms (2)

Buprenorphine/naloxone Microdosing

ACTIVE COMPARATOR

Participants with Opioid use disorder will receive a Buprenorphine/naloxone microdosing package from the ED. This will consist of a five-day take-home packages with gradually increasing doses of 2mg/0.5mg buprenorphine/naloxone tablet employing a four times daily dosing schedule over five days. Day 1: Buprenorphine 0.5 mg-naloxone 0.125 mg SL\* QID\*\* (One quarter tablet), Day 2: Buprenorphine 1 mg-naloxone 0.25 mg SL QID (One half tablet), Day 3: Buprenorphine 2 mg-naloxone 0.5 mg SL QID (1 tablet), Day 4: Buprenorphine 3 mg-naloxone 0.75 mg SL QID (1.5 tablets) Day 5: Buprenorphine 16 mg-naloxone 4 mg SL once daily (8 tablets). \*SL: Sublingual \*\* QID: four times daily

Drug: Buprenorphine/naloxone

Buprenorphine/naloxone Standard Dosing

ACTIVE COMPARATOR

The control intervention will be provision of a buprenorphine/naloxone standard dosing package from the ED. This will consist of a five day package with a commonly accepted standard dosing regimen aiming to achieve a therapeutic buprenorphine/naloxone dose within 24 hours of initiation. Standard dosing packages are currently available in EDs in BC and Alberta as standard of care. Day 1: Buprenorphine 2 mg-naloxone 0.5 mg SL q1h prn to a maximum of 6 tablets in the first 24 hours (1 tablet), Day 2: Buprenorphine 12 mg-naloxone 3 mg SL once daily (6 tablets), Day 3: Buprenorphine 16 mg-naloxone 3 mg SL once daily (8 tablets), Day 4:Buprenorphine 16 mg-naloxone 3 mg SL once daily (8 tablets). Day 5:Buprenorphine 16 mg-naloxone 3 mg SL once daily (8 tablets).

Drug: Buprenorphine/naloxone

Interventions

Buprenorphine/naloxone DRUG

Buprenorphine/naloxone is a first line, evidence-based opioid agonist therapy that improves mortality for people with opioid use disorder, and that has been demonstrated to be effective at retaining people in addictions care and decreasing illicit opioid use when initiated from EDs.

Also known as: Suboxone

Buprenorphine/naloxone Microdosing; Buprenorphine/naloxone Standard Dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• We will include ED patients ≥18 years of age with opioid use disorder who are being discharged from the ED. We will define opioid use disorder as non-medical opioid use in the previous 30 days and a positive score for opioid dependency based on the validated Rapid Opioid Dependence Screen (RODS).
• All patients will also be assessed by the treating physician or degree of clinical opioid withdrawal, based on the clinical opiate withdrawal scale (COWS) score. Patients will be eligible for the take-home study interventions if they have a COWS score \<=12, as a score greater than 12 would mean the patient is a candidate for standard buprenorphine induction in the ED at that moment in time, and would therefore not be eligible for outpatient study interventions.

You may not qualify if:

• Active withdrawal at time of ED assessment (Clinical Opiate Withdrawal Score \[COWS\] \>12)
• Admitted to hospital
• Severe communication barriers that inhibit patients' understanding of study procedures and interventions
• Are taking opioids for cancer or palliative-care related indications
• Are deemed unsafe to approach by ED providers
• Incarceration
• Not a resident of the province in which they are seeking care (BC or Alberta)
• Actively receiving OAT, defined as having filled a prescription for one of the following medications in the 5 days prior to ED presentation: buprenorphine/naloxone, methadone, sustained release morphine, injectable hydromorphone, injectable diacetylmorphine
• Prior enrollment in the study
• Known or suspected mechanical gastrointestinal obstruction (e.g., bowel obstruction or strictures) or any diseases/conditions that affect bowel transit (e.g., ileus of any type).
• Suspected surgical abdomen (e.g., acute appendicitis or pancreatitis).
• Severe respiratory insufficiency.
• Severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury.
• Complicating patient factors that make home inductions from the ED unsafe and/or that require expert consultation for consideration of induction in an observed setting.
• These factors include:

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (6)

Foothills Medical Centre

Calgary, Alberta, T2N2T9, Canada

RECRUITING

Northeast Community Health Centre

Edmonton, Alberta, T5A 5E4, Canada

RECRUITING

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

NOT YET RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

University of British Columbia Hospital

Vancouver, British Columbia, V6T2B5, Canada

RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

Related Publications (3)

• Moe J, Badke K, Pratt M, Cho RY, Azar P, Flemming H, Sutherland KA, Harvey B, Gurney L, Lockington J, Brasher P, Gill S, Garrod E, Bath M, Kestler A. Microdosing and standard-dosing take-home buprenorphine from the emergency department: A feasibility study. J Am Coll Emerg Physicians Open. 2020 Oct 20;1(6):1712-1722. doi: 10.1002/emp2.12289. eCollection 2020 Dec.

  PMID: 33392580 BACKGROUND

• Moe J, Doyle-Waters MM, O'Sullivan F, Hohl CM, Azar P. Effectiveness of micro-induction approaches to buprenorphine initiation: A systematic review protocol. Addict Behav. 2020 Dec;111:106551. doi: 10.1016/j.addbeh.2020.106551. Epub 2020 Jul 11.

  PMID: 32739588 BACKGROUND

• Moe J, O'Sullivan F, Hohl CM, Doyle-Waters MM, Ronsley C, Cho R, Liu Q, Azar P. Short communication: Systematic review on effectiveness of micro-induction approaches to buprenorphine initiation. Addict Behav. 2021 Mar;114:106740. doi: 10.1016/j.addbeh.2020.106740. Epub 2020 Nov 25.

  PMID: 33352498 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Jessica Moe, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elle Wang, MSc

CONTACT

6046152538; seth.long@ubc.ca

Cindy Liu, BSc

CONTACT

778-929-1281; elle.wang@ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor UBC Department of Emergency Medicine

Model Details: Patients will be randomized to receive either a microdosing package or standard dosing package, using permuted blocks of variable sizes (2 and 4). We will stratify randomization by study site.

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 19, 2021
• Study Start: July 23, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)