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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Comparing Rapid Micro-Induction and Standard Induction of Buprenorphine/Naloxone for Treatment of Opioid Use Disorder: A Randomized Controlled Trial

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Buprenorphine/naloxone
* Drug: Hydromorphone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapid Micro-Induction<br>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<br>* Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered via sublingual tablet form.<br>* Other names: Suboxone;Drug: Hydromorphone<br>* 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.<br>* Other names: Dihydromorphinone, Dilaudid;|
| Active Comparator: Standard Induction<br>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<br>* Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered via sublingual tablet form.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Buprenorphine/naloxone, Suboxone, Opioid agonist treatment, Micro-induction, Microdosing, Withdrawal Management