# Safety and Efficacy of High Dose Buprenorphine Induction in Fentanyl Positive Emergency Department Patients

> **NIH NIH UG3** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $678,662

## Abstract

Summary
This UG3/UH3 is based on the need to identify optimal induction strategies for buprenorphine (BUP) in
patients’ with untreated opioid use disorder (OUD). Prior BUP induction studies and guidelines including those
from the Substance Abuse and Mental Health Services Administration, the American Society of Addiction
Medicine and the American College of Emergency Medicine differ with regard to BUP dosing for treatment
induction. Furthermore, existing guidelines were developed before the proliferation of fentanyl in the illicit drug
supply. Recently, reports have raised concerns that patients with OUD using fentanyl have more difficulty with
BUP induction with more worsening/precipitated withdrawal events. These concerns have led to a proliferation
of BUP induction strategies that range from low–and-slow “micro-dosing” to rapid “supra-therapeutic” BUP
dosing. This proposal aims to determine whether standard buprenorphine induction results in more
worsening/precipitated withdrawal events in fentanyls-positive users than other opioid-dependent patients and
to examine the safety, tolerability, acceptability and clinical effectiveness of a single high dose BUP induction
strategy in Emergency Department (ED) patients with untreated OUD.
UG3 specific aims. Aim 1a. First we will develop and manualized escalating high dose BUP induction
protocols that can be delivered with high fidelity in the ED. 1b. Then we will evaluate the safety and tolerability
of escalating initial BUP dose in three 10-person cohorts (16mg, 24mg, 32mg) of fentanyl positive ED patients
with untreated OUD meeting criteria for ED initiated BUP. 1c. We will collect data on patient centered and
operational outcomes including patient satisfaction, need for rescue BUP doses and ancillary medications. Aim
2. Perform a pilot multicenter RCT of high versus standard BUP induction at four sites with well-established ED
BUP initiation programs to prove feasibility and validate patient satisfaction. 2a. Compare the optimal high
dose induction strategy from Aim 1 to a “standard” ED induction strategy in 80 (20 per site) fentanyl positive
ED patients meeting criteria for ED initiated BUP randomized 1:1. 2b. Assess the primary composite outcome
of precipitated/worsening withdrawal in each study arm. 2c. Compare secondary patient centered and
operational outcomes in each study arm.
UH3 specific aims. Aim 1a. In a multicenter RCT performed at the four UG3 sites, compare high versus
standard dose BUP induction randomized 1:1 on the primary composite outcome of worsening/precipitated
withdrawal in 708 patients. Aim 2a. Compare high-dose BUP induction to standard BUP induction on the
clinical efficacy outcome of engagement in comprehensive addiction treatment at 7-days post BUP induction.
2b. Compare patient centered and implementation outcomes between study arms.

## Key facts

- **NIH application ID:** 10525271
- **Project number:** 1UG3DA056891-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Ethan Adrian Cowan
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $678,662
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525271

## Citation

> US National Institutes of Health, RePORTER application 10525271, Safety and Efficacy of High Dose Buprenorphine Induction in Fentanyl Positive Emergency Department Patients (1UG3DA056891-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10525271. Licensed CC0.

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