This study was a 24-week, open-label, randomized controlled, comparative effectiveness trial at eight U.S. community-based inpatient services and followed up participants as outpatients. Participants were 18 years of age or older, met Diagnostic and Statistical Manual of Mental Disorders-5 criteria for 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 randomization (1:1) to receive extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (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.

Between 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. 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) favored BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population.

This study is supported by the National Institute on Drug Abuse (NCT02032433).