Identifying Optimal Buprenorphine Dosing for Opioid Use Disorder Treatment and Prevention of Overdose (Optimal Bup)

Randomized Clinical Trial of a 16 mg vs. 24 mg Maintenance Daily Dose of Buprenorphine to Increase Retention in Treatment Among People With Opioid Use Disorder

The investigators aim to test the effectiveness of a high maintenance daily dose of buprenorphine (24 mg) for improving outcomes among patients who used fentanyl compared to the standard daily dose (16 mg).

The main question it aims to answer is: will patients who are randomly assigned to the high 24 mg maintenance dose, as compared to patients randomly assigned to the standard 16 mg maintenance dose, have improved retention in buprenorphine treatment (primary outcome), decreased use of non-prescribed opioids (secondary outcome), decreased opioid cravings (secondary outcome), and decreased risk of fatal and non-fatal opioid overdose (secondary outcome).

Study Overview

• Status: Not yet recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Buprenorphine

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alyssa Peachey, MHA; Phone Number: 401-808-6950; Email: alyssa_peachey@brown.edu
• Study Contact Backup: Name: Rachel Wightman, MD; Email: rachel_wightman@brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English-speaking
• Age 18 years-old or older
• Identified by the treating physician as having moderate to severe opioid use disorder (OUD)
• Initiating or continuing buprenorphine for treatment of opioid use disorder
• History of fentanyl use (confirmed by fentanyl positive urine drug screen (UDS) at intake OR if on buprenorphine maintenance treatment fentanyl plus a positive UDS within the last month OR self- reported ongoing fentanyl use during treatment)

Exclusion Criteria:

• Previous enrollment in the trial
• Incarcerated or in police custody
• Pregnant
• Live outside of Rhode Island (RI)
• Unable to provide informed consent
• Allergy to Buprenorphine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Maintenance Daily Dose (24mg); The experimental intervention is a high daily maintenance dose of buprenorphine (24 mg) plus any usual clinical care the participant receives at the clinic. This high daily dose is the upper limit of the FDA-approved dose range 35-37 and was selected based on preclinical studies, clinician anecdotes, case reports, and retrospective analyses suggesting improved effectiveness of higher buprenorphine doses among patients with a history of fentanyl use. Underlying pharmacodynamic principles support that the 24 mg daily dose of buprenorphine is likely to be well-tolerated, safe, and better control cravings among people with a history of fentanyl use.	Drug: Buprenorphine; Buprenorphine in a highly effective treatment for opioid use disorder (OUD). Buprenorphine dose guidelines for OUD treatment were determined by clinical trials conducted in populations with a history of heroin use. However, fentanyl is changing the calculation of treatment, and optimal buprenorphine dosing for people who use fentanyl is unknown.
Active Comparator: Standard Maintenance Daily Dose (16mg); The control intervention is the FDA-recommended target daily maintenance dose of buprenorphine (16 mg) plus any usual clinical care the participant receives at the clinic.	Drug: Buprenorphine; Buprenorphine in a highly effective treatment for opioid use disorder (OUD). Buprenorphine dose guidelines for OUD treatment were determined by clinical trials conducted in populations with a history of heroin use. However, fentanyl is changing the calculation of treatment, and optimal buprenorphine dosing for people who use fentanyl is unknown.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Engagement	The primary outcome is the percentage of participants retained in buprenorphine treatment. Participants will be classified as retained in buprenorphine treatment at six months post- randomization if (1) the study site data indicate that they remained engaged in treatment or (2) the PDMP suggest that they continued treatment elsewhere and have not had a gap of more than 27 days in medication on-hand based on fill dates and days' supply.	six months post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of non-prescribed opioids	Non-prescribed fentanyl and other opioid use will be assessed via urine drug screens (UDS) plus fentanyl test strip assessment on a monthly basis for six months after study enrollment.	six months post-randomization
Control of Opioid Cravings	Measured using patient reported outcomes via the Opioid Craving Scale, a reliable, validated scale for people with opioid use disorder. The scale consists of three questions related to opioid cravings rated on a scale of 1-10 with 1 being not at all and 10 being extremely. A higher score denotes increased opioid cravings.	six months post-randomization
Rate of Non-fatal or Fatal Opioid Overdose	Non-fatal and fatal opioid overdoses will be assessed using statewide data from the Rhode Island Department of Health, including the Emergency Medical Services (EMS) Information System, Opioid Overdose Reporting System (OORS), and Office of the State Medical Examiners (OSME). All of these systems report non-fatal or fatal opioid overdoses which investigators will aggregate to arrive at the rate of non-fatal or fatal opioid overdoses.	twelve months post-randomization
Use of non-prescribed opioids	Non-prescribed fentanyl and other opioid use will self reported via a Time Line Followback (TLFB) assessing ongoing non-prescribed opioid/fentanyl use at 1, 3, and 6 months.	six months post-randomization

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Collaborators: Brown University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: STUDY00000075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No