search
Back to results

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

Primary Purpose

Opioid Use Disorder

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Buprenorphine/naloxone
Hydromorphone
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use Disorder focused on measuring Buprenorphine/naloxone, Suboxone, Opioid agonist treatment, Micro-induction, Microdosing, Withdrawal Management

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  1. Diagnosis of severe medical or psychiatric conditions contraindicated for buprenorphine/naloxone or hydromorphone treatment;
  2. Anticipated deterioration of health due to discontinuation of medications that are contraindicated with buprenorphine/naloxone and/or hydromorphone;
  3. Positive pregnancy test for women of childbearing potential;
  4. Methadone use in the past 5 days;
  5. Buprenorphine use in the past 5 days;
  6. Known allergy or sensitivity to buprenorphine/naloxone and/or hydromorphone;
  7. 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;
  8. Unwilling or unable to use an effective method of birth control approved by the study investigators throughout the study.

Sites / Locations

  • Vancouver General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rapid Micro-Induction

Standard Induction

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Illicit drug use
Assessed by urine drug screens (UDS) and Treatment Outcomes Profile (TOP).
Drug use behaviour
Assessed by the Treatment Outcomes Profile (TOP).
Treatment retention
Participants who pick up their prescription of bup/nx on Day 7. Assessed via the pharmacy database.
Craving
Assessed by the numeric craving scale.
Pain
Assessed by the numeric pain scale.
Physical health
Assessed by the health section of the Opiate Treatment Index (OTI).
Client satisfaction
Assessed by the Treatment Perceptions Questionnaire (TPQ).
Appearance of adverse events
Assessed by an adverse events report form.

Full Information

First Posted
January 13, 2020
Last Updated
October 5, 2022
Sponsor
University of British Columbia
Collaborators
Vancouver Coastal Health
search

1. Study Identification

Unique Protocol Identification Number
NCT04234191
Brief Title
Comparing Rapid Micro-Induction and Standard Induction of Buprenorphine/Naloxone for Treatment of Opioid Use Disorder
Official Title
Comparing Rapid Micro-Induction and Standard Induction of Buprenorphine/Naloxone for Treatment of Opioid Use Disorder: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 18, 2021 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
Collaborators
Vancouver Coastal Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder
Keywords
Buprenorphine/naloxone, Suboxone, Opioid agonist treatment, Micro-induction, Microdosing, Withdrawal Management

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rapid Micro-Induction
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard Induction
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Buprenorphine/naloxone
Other Intervention Name(s)
Suboxone
Intervention Description
Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered via sublingual tablet form.
Intervention Type
Drug
Intervention Name(s)
Hydromorphone
Other Intervention Name(s)
Dihydromorphinone, Dilaudid
Intervention Description
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.
Primary Outcome Measure Information:
Title
Successful induction of bup/nx with low levels of withdrawal
Description
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.
Time Frame
Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Secondary Outcome Measure Information:
Title
Illicit drug use
Description
Assessed by urine drug screens (UDS) and Treatment Outcomes Profile (TOP).
Time Frame
Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Title
Drug use behaviour
Description
Assessed by the Treatment Outcomes Profile (TOP).
Time Frame
Baseline to Day 1 (Standard Induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Title
Treatment retention
Description
Participants who pick up their prescription of bup/nx on Day 7. Assessed via the pharmacy database.
Time Frame
Day 7
Title
Craving
Description
Assessed by the numeric craving scale.
Time Frame
Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Title
Pain
Description
Assessed by the numeric pain scale.
Time Frame
Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Title
Physical health
Description
Assessed by the health section of the Opiate Treatment Index (OTI).
Time Frame
Baseline (both arms)
Title
Client satisfaction
Description
Assessed by the Treatment Perceptions Questionnaire (TPQ).
Time Frame
Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)
Title
Appearance of adverse events
Description
Assessed by an adverse events report form.
Time Frame
Baseline to Day 1 (Standard induction Arm) or Day 2 (Rapid Micro-Induction Arm)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pouya Azar, MD, FRCPC, DABAM
Phone
604-875-4111
Ext
54788
Email
pouya.rezazadeh-azar@ubc.ca
First Name & Middle Initial & Last Name or Official Title & Degree
James Wong, MSc
Phone
604-875-5823
Email
james.wong@vch.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pouya Azar, MD, FRCPC, DABAM
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nickie Mathew, MD, MSc, FRCPC, ABPN, ABPM
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pouya Azar, MD, FRCPC, DABAM
Phone
604-875-4111
Ext
54788
Email
pouya.rezazadeh-azar@ubc.ca

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to make individual participant data available to other researchers.
Citations:
PubMed Identifier
35005396
Citation
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.
Results Reference
background
PubMed Identifier
30901127
Citation
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.
Results Reference
background
PubMed Identifier
27499655
Citation
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.
Results Reference
background
PubMed Identifier
31046631
Citation
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.
Results Reference
background
PubMed Identifier
26406300
Citation
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.
Results Reference
background
PubMed Identifier
33579359
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs