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| Name | Class |
|---|---|
| Vancouver Coastal Health | OTHER_GOV |
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The current first-line treatment for opioid use disorder (OUD) in Canada is buprenorphine/naloxone (bup/nx). The standard induction method of bup/nx requires patients to be abstinent from opioids and thereby experience withdrawal symptoms prior to induction, which can be a major barrier in starting treatment. Rapid micro-induction (also known as micro-dosing, low-dose induction) involves the administration of small, frequent does of bup/nx and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of bup/nx in patients with OUD.
This is a randomized, controlled, open-label superiority trial involving 50 individuals with OUD. Participants will be randomized into two arms: rapid micro-induction and standard induction (based on the American Society of Addiction Medicine Practice Guidelines and product monograph) of bup/nx.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rapid Micro-Induction | Experimental | On Day 1, participants will receive 0.5mg bup/nx sublingually (SL) every 3 hours (Q3H) - total daily dose of 4mg. On Day 2, they will receive 1mg bup/nx SL Q3H - total daily dose of 8mg. On Day 3, they will receive 8mg bup/nx SL once and 1-4mg bup/nx SL Q3H as needed (PRN) for withdrawal symptoms and/or craving and/or pain - maximum daily dose of 32mg. Afterwards, their day 3 total dose will be consolidated to once daily dosing - maximum daily dose of 32mg. On Days 1 and 2, participants will concurrently receive 1-48mg hydromorphone orally, intravenously, subcutaneously, or intramuscularly (PO/IV/SC/IM) Q1 to 3H PRN for withdrawal symptoms and/or craving and/or pain, titrated to effect (start at lower end of dosing range). Hydromorphone will be discontinued on Days 3 onwards. |
|
| Standard Induction | Active Comparator | Day 1 is initiated when participants score 11 or above on the Clinical Opiate Withdrawal Scale (COWS), and when they have been abstinent from short-acting opioids for at least 6-12 hours or from long-acting opioids for 24-72 hours. On Day 1, participants will start with 2 or 4mg bup/nx SL. If their COWS score increases, bup/nx will be held. If their COWS score remains the same or decreases, additional dosing can be done in increments of 2mg bup/nx SL every 2 hours (Q2H) as needed (PRN). On Day 2, dosing will be consolidated to once daily dosing. The maximum total daily dose for Day 1 and 2 is 32mg. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Buprenorphine/naloxone | Drug | Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered via sublingual tablet form. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Successful induction of bup/nx with low levels of withdrawal | This is defined as the following: participants who remain in treatment until they have received a total daily dose of ≥ 8mg of bup/nx (successful induction), and score ≤ 12 on the COWS (low levels of withdrawal) from baseline to when they reach that dose. | Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Measure | Description | Time Frame |
|---|---|---|
| Illicit drug use | Assessed by urine drug screens (UDS) and Treatment Outcomes Profile (TOP). | Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Drug use behaviour |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pouya Azar, MD, FRCPC, DABAM | Contact | 604-875-4111 | 54788 | pouya.rezazadeh-azar@ubc.ca |
| James Wong, MSc | Contact | 604-875-5823 | james.wong@vch.ca |
| Name | Affiliation | Role |
|---|---|---|
| Pouya Azar, MD, FRCPC, DABAM | University of British Columbia | Principal Investigator |
| Nickie Mathew, MD, MSc, FRCPC, ABPN, ABPM | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vancouver General Hospital | Recruiting | Vancouver | British Columbia | V5Z 1M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35005396 | Background | Sandhu R, Zivanovic R, Klaire S, Nikoo M, Rozylo J, Azar P. Buprenorphine/naloxone induction for treatment of acute on chronic pain using a micro-dosing regimen: A case report. Can J Pain. 2019 Apr 25;3(1):79-84. doi: 10.1080/24740527.2019.1599279. eCollection 2019. | |
| 30901127 | Background | Klaire S, Zivanovic R, Barbic SP, Sandhu R, Mathew N, Azar P. Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series. Am J Addict. 2019 Jul;28(4):262-265. doi: 10.1111/ajad.12869. Epub 2019 Mar 22. |
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There is no plan to make individual participant data available to other researchers.
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000069479 | Buprenorphine, Naloxone Drug Combination |
| D004091 | Hydromorphone |
| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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|
| Hydromorphone | Drug | Hydromorphone is an opioid used for managing pain, craving, and withdrawal. It is administered orally via tablet or liquid form; or administered intravenously, subcutaneously, or intramuscularly via liquid form. |
|
|
Assessed by the Treatment Outcomes Profile (TOP).
| Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Treatment retention | Participants who pick up their prescription of bup/nx on Day 7. Assessed via the pharmacy database. | Day 7 |
| Craving | Assessed by the numeric craving scale. | Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Pain | Assessed by the numeric pain scale. | Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Physical health | Assessed by the health section of the Opiate Treatment Index (OTI). | Baseline (both arms) |
| Client satisfaction | Assessed by the Treatment Perceptions Questionnaire (TPQ). | Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| Appearance of adverse events | Assessed by an adverse events report form. | Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm) |
| 27499655 | Background | Hammig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, Dursteler KM, Vogel M. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil. 2016 Jul 20;7:99-105. doi: 10.2147/SAR.S109919. eCollection 2016. |
| 31046631 | Background | Vogel M, Kock P, Strasser J, Wiesbeck G, Walter M, Dursteler KM. Chronic High-Dose Buprenorphine Does Not Block Subjective High from Diacetylmorphine in a Patient in Heroin-Assisted Treatment. J Psychoactive Drugs. 2019 Sep-Oct;51(4):377-382. doi: 10.1080/02791072.2019.1610200. Epub 2019 May 2. |
| 26406300 | Background | Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. 2015 Sep-Oct;9(5):358-67. doi: 10.1097/ADM.0000000000000166. |
| 33579359 | Derived | Wong JSH, Nikoo M, Westenberg JN, Suen JG, Wong JYC, Krausz RM, Schutz CG, Vogel M, Sidhu JA, Moe J, Arishenkoff S, Griesdale D, Mathew N, Azar P. Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial. Addict Sci Clin Pract. 2021 Feb 12;16(1):11. doi: 10.1186/s13722-021-00220-2. |
| D006571 |
| Heterocyclic Compounds |
| D009270 | Naloxone |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D009022 | Morphine Derivatives |