MiBUP: A pilot randomized controlled trial of low-dose initiation of buprenorphine for opioid use disorder: Design and rationale.

Background: Buprenorphine is an effective treatment for opioid use disorder (OUD), however withdrawal during initiation is a barrier. Low-dose initiation (LDI) involves starting very small doses of buprenorphine overlapping with opioids to avoid withdrawal. This pilot study aims to evaluate the feasibility of a randomized controlled trial (RCT) comparing buprenorphine LDI versus standard initiation among ambulatory patients with OUD. Methods: This is a pragmatic parallel-group open-label pilot RCT of LDI versus standard initiation in ambulatory settings. LDI arm: starts with 0.5-0.125 mg of sublingual buprenorphine-naloxone films daily, titrating to a therapeutic dose over eight days. Standard arm: participants achieve moderate withdrawal before beginning with 4-1 mg. Therapeutic target in both arms:16-4 mg to 32-8 mg. A total of 70 adults (18 years or older) with any severity of OUD will be recruited. Key exclusion includes currently taking medication treatment for OUD, severe alcohol or benzodiazepine use disorder, severe mental illness, and pregnancy. The primary outcome: feasibility of recruiting primary care patients with OUD to a clinical trial of LDI, measured as percent of assessed participants who enroll in the study. Key secondary outcomes: LDI protocol feasibility, meaning compliance to the protocol (i.e., starting with less than 1 mg of buprenorphine and taking increasing dosages daily); preliminary effectiveness of treatment uptake at a two-week study visit, confirmed by a urine drug test positive for buprenorphine; six-week treatment retention measured by pharmacy-dispensed buprenorphine; and safety outcomes. Discussion: As a pilot clinical trial this study will inform design of a fully powered RCT to test buprenorphine LDI in the ambulatory setting.Trial registrationClinicalTrials.gov, NCT05450718: date of registration: June 22, 2022; https://clinicaltrials.gov/study/NCT05450718?term=NCT05450718&rank=1.