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

James S H Wong, Mohammadali Nikoo, Jean N Westenberg, Janet G Suen, Jennifer Y C Wong, Reinhard M Krausz, Christian G Schütz, Marc Vogel, Jesse A Sidhu, Jessica Moe, Shane Arishenkoff, Donald Griesdale, Nickie Mathew, Pouya Azar, James S H Wong, Mohammadali Nikoo, Jean N Westenberg, Janet G Suen, Jennifer Y C Wong, Reinhard M Krausz, Christian G Schütz, Marc Vogel, Jesse A Sidhu, Jessica Moe, Shane Arishenkoff, Donald Griesdale, Nickie Mathew, Pouya Azar

Abstract

Background: Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone 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 buprenorphine/naloxone in patients with OUD.

Methods: This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is the completion of buprenorphine/naloxone induction with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction.

Discussion: This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis. Trial registration ClinicalTrials.gov, NCT04234191; date of registration: January 21, 2020; https://ichgcp.net/clinical-trials-registry/NCT04234191.

Keywords: Buprenorphine/naloxone; Micro-induction; Microdosing; Opioid agonist treatment; Opioid use disorder; Suboxone.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study schema

References

    1. Hall WD, Farrell M. Reducing the opioid overdose death toll in North America. PLoS Med. 2018;15:e1002626. doi: 10.1371/journal.pmed.1002626.
    1. Ottawa: Public Health Agency of Canada. Opioid-related harms in Canada. 2020. .
    1. Krausz MR, Wong JSH, Moazen-Zadeh E, Jang KL. Been there, done that: lessons from Vancouver’s efforts to stem the tide of overdose deaths. Can J Psychiatry. 2020 doi: 10.1177/0706743720912860.
    1. Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States, 1999–2018. 2020.
    1. Ye X, Sutherland J, Henry B, Tyndall M, Kendall PRW. At-a-glance—impact of drug overdose-related deaths on life expectancy at birth in British Columbia TT (Aperçu—impact des décès par surdose de drogue sur l’espérance de vie à la naissance en Colombie-Britannique) Health Promot Chronic Dis Prev Can Res Policy Pract. 2018;38:248–251. doi: 10.24095/hpcdp.38.6.05.
    1. Degenhardt L, Charlson F, Ferrari A, Santomauro D, Erskine H, Mantilla-Herrara A, et al. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Psychiatry. 2018;5:987–1012. doi: 10.1016/S2215-0366(18)30337-7.
    1. American Society of Addiction Medicine. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med. 2020;14. .
    1. Bruneau J, Ahamad K, Goyer M-È, Poulin G, Selby P, Fischer B, et al. Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018;190:E247–E257. doi: 10.1503/cmaj.170958.
    1. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 doi: 10.1002/14651858.CD002207.pub4.
    1. Whelan PJ, Remski K. Buprenorphine vs methadone treatment: a review of evidence in both developed and developing worlds. J Neurosci Rural Pract. 2012;3:45–50. doi: 10.4103/0976-3147.91934.
    1. Orman JS, Keating GM. Buprenorphine/naloxone. Drugs. 2009;69:577–607. doi: 10.2165/00003495-200969050-00006.
    1. Mattick RP, Ali R, White JM, O’Brien S, Wolk S, Danz C. Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Addiction. 2003;98:441–452. doi: 10.1046/j.1360-0443.2003.00335.x.
    1. Azar P, Wong JSH, Jassemi S, Moore E, Vo DX, Nikoo M, et al. A case report: rapid micro-induction of buprenorphine/naloxone to administer buprenorphine extended-release in an adolescent with severe opioid use disorder. Am J Addict. 2020 doi: 10.1111/ajad.13050.
    1. Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, et al. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil. 2016;7:99–105. doi: 10.2147/SAR.S109919.
    1. Lee DS, Hann JE, Klaire SS, Nikoo M, Negraeff MD, Rezazadeh-Azar P. Rapid induction of buprenorphine/naloxone for chronic pain using a microdosing regimen: a case report. A&A Pract. 2020;14:44–47. doi: 10.1213/XAA.0000000000001138.
    1. Randhawa PA, Brar R, Nolan S. Buprenorphine–naloxone “microdosing”: an alternative induction approach for the treatment of opioid use disorder in the wake of North America’s increasingly potent illicit drug market. CMAJ. 2020;192:E73. doi: 10.1503/cmaj.74018.
    1. 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;28:262–265. doi: 10.1111/ajad.12869.
    1. Rozylo J, Mitchell K, Nikoo M, Durante SE, Barbic SP, Lin D, et al. Case report: successful induction of buprenorphine/naloxone using a microdosing schedule and assertive outreach. Addict Sci Clin Pract. 2020;15:1–6. doi: 10.1186/s13722-020-0177-x.
    1. Ghosh SM, Klaire S, Tanguay R, Manek M, Azar P. A review of novel methods to support the transition from methadone and other full agonist opioids to buprenorphine/naloxone sublingual in both community and acute care settings. Can J Addict. 2019;10:41–50. doi: 10.1097/CXA.0000000000000072.
    1. Martin L, Lennox R, Regenstreif L, O’Shea T. Case report: “striving to skip the withdrawal” using buprenorphine-naloxone microdosing for hospitalized patients. Can J Addict. 2019;10:35–40. doi: 10.1097/CXA.0000000000000048.
    1. 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;3:79–84. doi: 10.1080/24740527.2019.1599279.
    1. Chiang CN, Hawks RL. Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug Alcohol Depend. 2003;70:S39–47. doi: 10.1016/S0376-8716(03)00058-9.
    1. Harrisa PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. Harrisa PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi: 10.1016/j.jbi.2019.103208.
    1. Olfson M, Zhang VS, Schoenbaum M, King M. Trends in buprenorphine treatment in the United States, 2009–2018. JAMA. 2020;323:276–277. doi: 10.1001/jama.2019.18913.
    1. De Wet CJ, Reed LJ, Bearn J. The rise of buprenorphine prescribing in England: analysis of NHS regional data, 2001–03. Addiction. 2005;100:495–499. doi: 10.1111/j.1360-0443.2005.01039.x.
    1. Benyamina A. The current status of opioid maintenance treatment in France: a survey of physicians, patients, and out-of-treatment opioid users. Int J Gen Med. 2014;7:449–457. doi: 10.2147/IJGM.S61014.
    1. Indivior UK Limited. SUBOXONE® (buprenorphine and naloxone) product monograph. Berkshire; 2007.
    1. Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS) J Psychoact Drugs. 2003;35:253–259. doi: 10.1080/02791072.2003.10400007.
    1. Marsden J, Farrell M, Bradbury C, Dale-Perera A, Eastwood B, Roxburgh M, et al. Development of the treatment outcomes profile. Addiction. 2008;103:1450–1460. doi: 10.1111/j.1360-0443.2008.02284.x.
    1. Lazaridou A, Elbaridi N, Edwards RR, Berde CB. Chapter 5—pain assessment. In: Benzon HT, Raja SN, Liu SS, Fishman SM, editors. Cohen SPBT-E of PM. 4. Amsterdam: Elsevier; 2018. pp. 39.e1–46.e1.
    1. Darke S, Ward J, Hall W, Heather N, Wodak A. The opiate treatment index (OTI) manual. Technical Report 11). Sydney, Australia: National Drug and Alcohol Research; 1991.
    1. Marsden J, Stewart D, Gossop M, Rolfe A, Bacchus L, Griffiths P, et al. Assessing client satisfaction with treatment for substance use problems and the development of the treatment perceptions questionnaire (TPQ) Addict Res. 2000;8:455–470. doi: 10.3109/16066350009005590.
    1. ICH. Clinical Safety Data Management: Definitions and Standards for Expedited Reporting E2A [Internet]. 1994. Available from:
    1. BC Coroners Service. Illicit drug toxicity deaths in BC: January 1, 2020–September 30, 2020. 2020. .
    1. Zoorob M. Fentanyl shock: the changing geography of overdose in the United States. Int J Drug Policy. 2019;70:40–46. doi: 10.1016/j.drugpo.2019.04.010.
    1. Morales KB, Park JN, Glick JL, Rouhani S, Green TC, Sherman SG. Preference for drugs containing fentanyl from a cross-sectional survey of people who use illicit opioids in three United States cities. Drug Alcohol Depend. 2019;204:107547. doi: 10.1016/j.drugalcdep.2019.107547.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi