Comparing Rapid Micro-Induction and Standard Induction of Buprenorphine/Naloxone for Treatment of Opioid Use Disorder

NCT04234191 | Recruiting Phase 2 DMC

• 1 other identifier: H19-03254
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Opioid Use Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (8)

• Illicit drug use

  Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm)

• Drug use behaviour

  Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm)

• Treatment retention

  Day 7

• Craving

  Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)

• Pain

  Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)

Study Arms (2)

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.

Drug: Buprenorphine/naloxone; Drug: Hydromorphone

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.

Drug: Buprenorphine/naloxone

Interventions

Buprenorphine/naloxone DRUG

Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered via sublingual tablet form.

Also known as: Suboxone

Rapid Micro-Induction; Standard Induction

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.

Also known as: Dihydromorphinone, Dilaudid

Rapid Micro-Induction

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Opioid Use Disorder (OUD) as defined by the Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria;
• Individuals seeking Opioid Agonist Treatment (OAT);
• Be 19 years of age or older;
• Be willing and able to adhere to the study protocol and follow-up schedule;
• Be able to provide written informed consent to participate in the clinical trial.
• If female and of childbearing potential, agree to use an effective method of birth control approved by the study investigators throughout the study.

You may not qualify if:

• Diagnosis of severe medical or psychiatric conditions contraindicated for buprenorphine/naloxone or hydromorphone treatment;
• Anticipated deterioration of health due to discontinuation of medications that are contraindicated with buprenorphine/naloxone and/or hydromorphone;
• Positive pregnancy test for women of childbearing potential;
• Methadone use in the past 5 days;
• Buprenorphine use in the past 5 days;
• Known allergy or sensitivity to buprenorphine/naloxone and/or hydromorphone;
• Anticipation that the patient may need to initiate pharmacological treatment during the trial that is deemed unsafe by the study physician or could prevent study completion;
• Unwilling or unable to use an effective method of birth control approved by the study investigators throughout the study.

Sponsors & Collaborators

• University of British Columbia: lead
• Vancouver Coastal Health: collaborator

Study Sites (1)

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Related Publications (6)

• 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.

  PMID: 35005396 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.

  PMID: 30901127 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.

  PMID: 27499655 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.

  PMID: 31046631 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.

  PMID: 26406300 BACKGROUND

• 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.

  PMID: 33579359 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination; Hydromorphone

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; Morphine Derivatives

Study Officials

• Pouya Azar, MD, FRCPC, DABAM

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Nickie Mathew, MD, MSc, FRCPC, ABPN, ABPM

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pouya Azar, MD, FRCPC, DABAM

CONTACT

604-875-4111; pouya.rezazadeh-azar@ubc.ca

James Wong, MSc

CONTACT

604-875-5823; james.wong@vch.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 21, 2020
• Study Start: August 18, 2021
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)