Rapid Outpatient Low-dose Initiation of Buprenorphine for OUD With Fentanyl Use (ROLDI)

Rapid Outpatient Low-dose Initiation of Buprenorphine for Individuals With OUD Using Fentanyl

The goal of this clinical trial is to learn if buprenorphine can be started for opioid use disorder with fentanyl use without requiring or precipitating opioid withdrawal. To be eligible, participants must have moderate or severe opioid use disorder and must have fentanyl detected on a urine drug test.

Participants will be admitted to a monitored research unit for the trial. They will be randomized to start buprenorphine with either standard initiation or with a new approach called rapid outpatient low-dose initiation (ROLDI).

For standard initiation, participants will be instructed to arrive to the unit with at least 8 hours since last fentanyl use. Once they have at least moderately severe opioid withdrawal (Clinical Opiate Withdrawal Scale [COWS] 11 or higher), participants will receive 2 mg, 2 mg, 4 mg, and then 8 mg sublingual buprenorphine, with doses every 2 hours. They will then continue 8 mg twice daily (or up to three times daily). This is the current standard of care.

For ROLDI, participants will not be required to have a period abstinence, they will have no or minimal withdrawal (COWS 4 or less) when starting buprenorphine, and participants will take 0.5 mg, 0.5 mg, 1 mg, 1 mg, 1 mg, and then 4 mg sublingual buprenorphine with dosing every two hours. They will then continue 8mg twice daily (or up to three times daily).

The main aim of this clinical trial is to assess whether ROLDI is safe, feasible, acceptable to patients, and worthwhile to study in a larger trial. The secondary aim is to describe fentanyl and norfentanyl pharmacokinetics (that is to say, fentanyl and norfentanyl concentration in blood and urine) during early abstinence to understand why some people using fentanyl develop precipitated withdrawal with standard initiation.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Buprenorphine

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kyle Kampman, MD; Phone Number: 215 746 2764; Email: kampman@pennmedicine.upenn.edu
• Study Contact Backup: Name: Ashish P Thakrar, MD, MS; Email: apthakrar@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Center for Studies of Addiction
      • Contact: Kyle M Kampman, MD; Phone Number: 1 215 746 2764; Email: kampman@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ages 18 or older
• Male, female, transgender, or non-binary
• DSM-5 criteria for opioid use disorder, moderate to severe
• Fentanyl positive on urine drug test
• Able to provide written informed consent in English prior to any study-related procedure

Exclusion Criteria:

• Pregnancy or actively lactating
• Previously documented hypersensitivity or allergy to buprenorphine or naloxone
• DSM-5 criteria for substance use disorder other than opioid use disorder (e.g., cannabis, cocaine, alcohol)
• Current benzodiazepine use
• Urine drug testing at screening positive for buprenorphine and/or methadone
• AST and/or ALT >3x upper limit of normal or total bilirubin >1.5x upper limit of normal
• eGFR <30 mL/min
• Use of CYP3A4-metabolized agents such as azole antifungals, macrolides, and protease inhibitors
• High risk of severe medetomidine withdrawal based on drug urine testing for medetomidine, prior withdrawal syndrome requiring intensive care unit admission, and/or patient-reported severe nausea/vomiting during early withdrawal, at the discretion of the study physicians.
• Significant medical symptoms (e.g. severe respiratory insufficiency), psychiatric symptoms, or dementia that, in the opinion of the investigators, would preclude compliance with the protocol, cooperation in the study, obtaining informed consent, or ability to safely participate in the study
• Pending legal action that could prohibit participation and/or compliance in study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapid outpatient low-dose initiation; Participants randomized to low-dose initiation will be instructed to arrive to the research unit without withdrawal. Participants with COWS <4 will be admitted to the research unit to begin induction. They will be administered 0.5, 0.5, 1, 1, 1, 4, and then 8 mg as sublingual buprenorphine films with doses scheduled every 2 hours. They will then continue 8mg twice daily (or up to three times daily) as maintenance treatment.	Drug: Buprenorphine; Sublingual buprenorphine
Active Comparator: Standard initiation; Participants randomized to standard induction will be instructed to arrive to the research unit with mild withdrawal and to have abstained from opioids for at least 8 hours, per ASAM Guidelines. Participants with COWS 4 or higher on initial assessment will be admitted to the research unit to begin induction. Standard initiation will follow guidelines from the 2020 Focused Update of the ASAM National Practice Guidelines. Once participants have had at least 8 hours of abstinence and have reached COWS 11 or greater, they will be given 2 mg sublingual buprenorphine, followed 2 hours later by 2 mg, followed 2 hours later by 4 mg, followed 2 hours later by 8 mg. They will then continue 8 mg twice (or up to three times) daily as maintenance treatment.	Drug: Buprenorphine; Sublingual buprenorphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initiation of buprenorphine maintenance without precipitated withdrawal	The proportion of subjects who complete buprenorphine initiation without precipitated withdrawal. Completing buprenorphine initiation is defined as reaching 8mg or more total daily dose of sublingual buprenorphine without termination of buprenorphine initiation for any reason. Precipitated withdrawal is defined as an increase in COWS of 6 or more (compared to the COWS immediately preceding the most recent dose of buprenorphine) within 2 hours of the most recent dose of sublingual buprenorphine.	10 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Estimated): August 29, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Fentanyl; Buprenorphine; Opioid addiction; Opiate; Low-dose initiation
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Buprenorphine
• Other Study ID Numbers: 855013

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No