Comparing Rapid Micro-Induction and Standard Induction of Buprenorphine/Naloxone for Treatment of Opioid Use Disorder
Study Details
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 (micro-dosing) 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 12mg bup/nx SL once and 1-4mg bup/nx SL Q3H as needed (PRN) - maximum daily dose of 24mg. On Day 4, their day 3 total dose will be consolidated to once daily dosing - maximum daily dose of 24mg. On Days 1 and 2, participants will concurrently receive 1-16mg hydromorphone orally, intravenously, subcutaneously, or intramuscularly (PO/IV/SC/IM) every 1-3 hours (Q1-3H) PRN to meet their opioid requirements, titrated to effect - maximum daily dose of 96mg. For the 1st dose of hydromorphone on Day 1, a maximum 8mg PO or 4mg SC/IV/IM dose will be given. Hydromorphone will be discontinued on Days 3 and 4. |
Drug: Buprenorphine/naloxone
Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered orally via sublingual tablet form.
Other Names:
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.
Other Names:
|
| Active Comparator: 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 2-4mg bup/nx SL. If they do not experience withdrawal symptoms 60-90 minutes after this dose, additional dosing can be done in increments of 2-4mg bup/nx SL. The suggested total dose target for Day 1 is 8-12mg. On Day 2, participants will start with a dose equal to the total amount of bup/nx SL administered on Day 1. The dose will be then titrated in increments or decrements of 2-8mg bup/nx SL to a level that holds the patient in treatment and suppresses opioid withdrawal. On Day 3, their day 2 total dose will be consolidated to once daily dosing. For both Days 2 and 3, the suggested total daily dose is at least 8mg, recommended 12-16mg, maximum daily dose of 24mg. |
Drug: Buprenorphine/naloxone
Buprenorphine/naloxone is an opioid agonist treatment for opioid use disorder. It is administered orally via sublingual tablet form.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Successful induction of bup/nx with low levels of withdrawal [Randomization to Day 3 (Standard Induction Arm) or Day 4 (Rapid Micro-Induction Arm)]
This is defined as the following: participants who remain in treatment until they have received a total daily dose of ≥ 12mg of bup/nx (successful induction), and score ≤ 12 on the COWS (low levels of withdrawal) from the time of randomization to when they reach that dose.
Secondary Outcome Measures
- Illicit drug use [Baseline (both arms), Day 3 (Standard Induction Arm), Day 4 (Rapid Micro-Induction Arm)]
Assessed by urine drug screens (UDS).
- Drug use behaviour [Baseline (both arms), Day 3 (Standard Induction Arm), Day 4 (Rapid Micro-Induction Arm)]
Assessed by the Treatment Outcomes Profile (TOP).
- Treatment retention [Day 5]
Participants who pick up their prescription of bup/nx on Day 7. Assessed via the pharmacy database.
- Craving [Baseline to Day 3 (both arms), Day 4 (Rapid Micro-Induction Arm)]
Assessed by a Visual analogue scale (0-10 scale).
- Pain [Baseline to Day 3 (both arms), Day 4 (Rapid Micro-Induction Arm)]
Assessed by a Visual analogue scale (0-10 scale).
- Physical health [Baseline (both arms)]
Assessed by the health section of the Opiate Treatment Index (OTI).
- Client satisfaction [Day 3 (Standard Induction Arm), Day 4 (Rapid Micro-Induction Arm)]
Assessed by the Treatment Perceptions Questionnaire (TPQ).
- Appearance of adverse events [Randomization to Day 3 (Standard Induction Arm) or Day 4 (Rapid Micro-Induction Arm)]
Assessed by an adverse events report form.
Eligibility Criteria
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;
-
Not experiencing mild to moderate opioid withdrawal after the last dose of methadone;
-
Positive urine test for methadone;
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vancouver General Hospital | Vancouver | British Columbia | Canada | V5Z 1M9 |
Sponsors and Collaborators
- University of British Columbia
- Vancouver Coastal Health
Investigators
- Principal Investigator: Pouya Azar, MD, FRCPC, DABAM, University of British Columbia
- Principal Investigator: Nickie Mathew, MD, FRCPC, ABPN, ABPM, University of British Columbia
Study Documents (Full-Text)
None provided.More Information
Publications
- Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, Dürsteler 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.
- 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.
- 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.
- 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.
- Vogel M, Köck P, Strasser J, Wiesbeck G, Walter M, Dürsteler 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.
- H19-03254