Rapid vs Standard Induction to Injectable Extended-Release Buprenorphine: A Randomized Clinical Trial.

Abstract

Standard induction (SI) using transmucosal buprenorphine-naloxone is challenging in individuals who inject opioids, use high doses of opioids, or use synthetic opioids (eg, fentanyl). To compare the effectiveness and safety of rapid induction (RI; single 4-mg dose of buprenorphine-naloxone) vs SI (≥7 days of buprenorphine-naloxone) followed by extended-release buprenorphine injection. This multicenter, open-label randomized clinical trial was conducted from October 26, 2021, to January 19, 2024, at 28 outpatient treatment centers in the US and Canada. Treatment-seeking participants with moderate or severe opioid use disorder who inject opioids, use high doses of opioids, or use fentanyl were studied. Participants were randomized 2:1 to RI or SI before 300-mg injection of extended-release buprenorphine. The primary end point, retention rate difference at injection 2 (1 week after injection 1), was estimated by a bayesian approach. Posterior probability was estimated for noninferiority of RI to SI (RI - SI >-10%) and superiority (RI - SI >0%). Adverse events (AEs), including investigator-assessed opioid withdrawal symptoms, were reported. Subgroup analyses compared participants with positive or negative fentanyl urine drug screen results. Analyses included 729 randomized participants (mean [SD] age, 40.7 [10.4] years; 406 [55.7%] male) who initiated transmucosal buprenorphine per protocol, including 474 in the RI arm and 255 in the SI arm. A total of 560 participants received extended-release buprenorphine injection 1 (409 [86.3%] in the RI arm and 151 [59.2%] in the SI arm), and 452 received injection 2 (314 [66.2%] in the RI arm and 138 [54.1%] in the SI arm). At injection 2, RI was noninferior with higher retention than SI (difference, 11.8%; 95% credible interval [CrI], 4.3%-19.0%; posterior probability greater than 0 was 99.9%). Similarly, among participants with a positive test result for fentanyl, the retention rate differential in favor of RI was 14.8% (95% CrI, 6.5%-23.7%; posterior probability greater than 0 was greater than 99.9%). AE incidence was not statistically different between RI and SI participants (202 [42.6%] vs 93 [35.5%]; difference, 6.1%; 95% CrI, -1.3% to 13.4%). Up to injection 2, most AEs were associated with opioid withdrawal. In this multicenter randomized clinical trial, RI had higher retention than SI overall and in patients who tested positive for fentanyl through extended-release buprenorphine injection 2. Administration of injection 2 after 1 week was well tolerated and minimized time below target therapeutic levels of 2 ng/mL or greater compared with injection after 1 month. ClinicalTrials.gov Identifier: NCT04995029.