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

NCT ID: NCT04234191

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-18
• Study Completion Date: 2025-01-31

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.

Conditions

Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapid Micro-Induction

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.

Group Type: EXPERIMENTAL

Buprenorphine/naloxone

Intervention Type: DRUG

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

Hydromorphone

Intervention Type: 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.

Standard Induction

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.

Group Type: ACTIVE_COMPARATOR

Buprenorphine/naloxone

Intervention Type: DRUG

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

Interventions

Buprenorphine/naloxone

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

Intervention Type: DRUG

Hydromorphone

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.

Intervention Type: DRUG

Other Intervention Names

Suboxone; Dihydromorphinone, Dilaudid

Eligibility Criteria

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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vancouver Coastal Health

OTHER_GOV

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Nickie Mathew

Clinical Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pouya Azar, MD, FRCPC, DABAM

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

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

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Pouya Azar, MD, FRCPC, DABAM

Role: CONTACT

pouya.rezazadeh-azar@ubc.ca

604-875-4111 ext. 54788

James Wong, MSc

Role: CONTACT

james.wong@vch.ca

604-875-5823

Facility Contacts

Pouya Azar, MD, FRCPC, DABAM

Role: primary

pouya.rezazadeh-azar@ubc.ca

604-875-4111 ext. 54788

References

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.

Reference Type: BACKGROUND

PMID: 35005396 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30901127 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27499655 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31046631 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26406300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33579359 (View on PubMed)

Other Identifiers

H19-03254

Identifier Type: -

Identifier Source: org_study_id