Dataset Information

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.

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://clinicaltrials.gov/ct2/show/NCT04234191.

SUBMITTER: Wong JSH

PROVIDER: S-EPMC7881636 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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.

Wong James S H JSH Nikoo Mohammadali M Westenberg Jean N JN Suen Janet G JG Wong Jennifer Y C JYC Krausz Reinhard M RM Schütz Christian G CG Vogel Marc M Sidhu Jesse A JA Moe Jessica J Arishenkoff Shane S Griesdale Donald D Mathew Nickie N Azar Pouya P

Addiction science & clinical practice 20210212 1

<h4>Background</h4>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 ...[more]

PMID: 33579359

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Project description:IntroductionAs fentanyl has become more readily available, opioid-related morbidity and mortality in the United States has increased dramatically. Preliminary studies suggest that high-affinity, partial mu-opioid receptor agonists such as the combination product buprenorphine-naloxone may reduce mortality from overdose and promote remission. With the escalating prevalence of opioid use disorder (OUD), it is essential to evaluate the effectiveness of opioid agonists like buprenorphine-naloxone. This study examines mortality and remission rates for OUD patients prescribed buprenorphine-naloxone to determine the efficacy of this treatment toward these outcomes.MethodsWe carried out a retrospective analysis using the US Collaborative Network database in TriNetX, examining de-identified medical records from nearly 92 million patients across 56 healthcare organizations. The study spanned the years from January 1, 2017-May 13, 2022. Cohort 1 included OUD patients who began buprenorphine-naloxone treatment within one-year post-diagnosis, while Cohort 2, the control group, consisted of OUD patients who were not administered buprenorphine. The study measured mortality and remission rates within a year of the index event, incorporating propensity score matching for age, gender, and race/ethnicity.ResultsPrior to propensity matching, we identified a total of 221,967 patients with OUD. Following exclusions, 61,656 patients treated with buprenorphine-naloxone showed 34% fewer deaths within one year of diagnosis compared to 159,061 patients who did not receive buprenorphine (2.6% vs 4.0%; relative risk [RR] 0.661; 95% confidence interval [CI] 0.627-0.698; P < 0.001). The remission rate was approximately 1.9 times higher in the buprenorphine-naloxone group compared to the control group (18.8% vs 10.1%; RR 1.862; 95% CI 1.812-1.914; P < 0.001). After propensity matching, the effect on mortality decreased but remained statistically significant (2.6% vs 3.0%; RR 0.868; 95% CI 0.813-0.927; P < 0.001) and the remission rate remained consistent (18.8% vs 10.4%; RR 1.812; 95% CI 1.750-1.876; P < 0.001). Number needed to treat for benefit was 249 for death and 12 for remission.ConclusionBuprenorphine-naloxone was associated with significantly reduced mortality and increased remission rates for patients with opioid use disorder and should be used as a primary treatment. The recognition and implementation of treatment options like buprenorphine-naloxone is vital in alleviating the impact of OUD.

Project description:BackgroundExtended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.MethodsWe initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.FindingsBetween Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).InterpretationIn this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.FundingNIDA Clinical Trials Network.

Project description:ImportanceOpioid-dependent patients often use the emergency department (ED) for medical care.ObjectiveTo test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine).Design, setting, and participantsA randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013.InterventionsAfter screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group.Main outcomes and measuresEnrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes.ResultsSeventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001).Conclusions and relevanceAmong opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption.Trial registrationclinicaltrials.gov Identifier: NCT00913770.

Dataset Information

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.

Background

Methods

Discussion

Publications

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.

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