Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial

Area of Science:

• Addiction Medicine
• Pharmacology
• Clinical Trials

Background:

• Injectable extended-release naltrexone (XR-naltrexone) is a key treatment for opioid use disorder (OUD).
• A significant barrier to XR-naltrexone initiation is the lengthy withdrawal period required from prior opioid treatments.
• Optimizing the initiation process can improve patient access and treatment adherence.

Purpose of the Study:

• To compare the effectiveness and safety of a rapid procedure (RP) versus the standard procedure (SP) for initiating XR-naltrexone in patients with OUD.
• To evaluate if RP can reduce the time and complexity associated with XR-naltrexone initiation.
• To assess opioid withdrawal symptoms and safety events during the initiation phase.

Main Methods:

• An optimized stepped-wedge cluster randomized trial involving 6 addiction treatment units.
• Participants with OUD were assigned to either the standard procedure (SP) or the rapid procedure (RP) based on the unit's assignment at admission.
• The RP involved a shorter buprenorphine taper, a single opioid-free day, and low-dose oral naltrexone with adjunctive medications, compared to the SP's longer opioid-free period.

Main Results:

• Successful XR-naltrexone initiation was significantly higher with the RP (62.7%) compared to the SP (35.8%).
• Opioid withdrawal severity did not significantly differ between the RP and SP groups.
• While infrequent, targeted safety events and serious adverse events were more common in the RP group, necessitating intensive monitoring.

Conclusions:

• The rapid procedure (RP) for initiating extended-release naltrexone (XR-naltrexone) is noninferior to the standard procedure (SP) in terms of effectiveness.
• RP significantly increases the rate of successful XR-naltrexone initiation, potentially improving treatment accessibility for opioid use disorder (OUD).
• While RP requires more intensive medical management and safety monitoring, it offers a time-saving alternative that could enhance the viability of XR-naltrexone treatment.