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

University of British Columbia

Status and phase: Enrolling; Phase 2

Conditions: Opioid Use Disorder

Treatments: Drug: Hydromorphone; Drug: Buprenorphine/naloxone

Study type: Interventional

Funder types: Other

Identifiers

NCT04234191

H19-03254

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Rapid Micro-Induction

Experimental group

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.

Treatment:

Drug: Buprenorphine/naloxone

Drug: Hydromorphone

Standard Induction

Active Comparator group

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.

Treatment:

Drug: Buprenorphine/naloxone