Buprenorphine Loading in the Emergency Department

Buprenorphine (BUP) is FDA-approved for the treatment of opioid withdrawal and opioid use disorder. Few ED providers have received the necessary DEA registration (aka X waiver) required to prescribe BUP, and urgent appointments to continue ongoing BUP treatment may not be readily available, thus leading to medication discontinuity. A loading dose induction strategy with 32mg of BUP may help effectively link ED patients to outpatient treatment while minimizing known barriers to ED uptake. Administering a "loading dose" of BUP to saturate mu-opioid receptors would extend the duration of action and provide additional time to secure ongoing treatment. Further, BUP's ceiling effect on respiratory depression makes it a remarkably safe drug even at high doses. In recent years, ED providers have begun to incorporate this approach into clinical protocols, however, it has not been formally studied in this clinical setting. The investigator's study represents the necessary step of studying this novel approach in the ED setting to define the parameters for clinical protocols and large-scale studies.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: Buprenorphine Naloxone

Detailed Description

A novel induction strategy, in which a loading dose of Buprenorphine (BUP) 32mg is administered, has the potential to mitigate barriers to treatment initiation. ED providers can treat patients with BUP for opioid withdrawal since DEA registration (X-waiver) is not required unless they wish to issue a prescription. Current BUP induction protocols, developed for inpatient and ambulatory care settings as well as for unobserved self- administration via prescription, usually recommend a first day dose of 8mg given in divided doses of 2- 4mg. However, patients discharged with ≤ 8mg SL total dose may experience return of withdrawal symptoms and/or opioid craving within only 4 hours.Treatment with a loading dose of 32mg in the ED may provide the necessary bridge treatment, relieving symptoms of withdrawal until a patient is able to attend a follow up appointment for further treatment.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.
• Meets DSM-5 criteria for moderate to severe OUD
• Has a positive urine screen for opioids and a negative urine screen for methadone
• Must be experiencing opioid withdrawal with a COWS score ≥8
• Is willing and able to participate in the study and follow study procedures
• Is able to provide adequate and reliable locator information for follow-up
• Has reliable access to a phone

Exclusion Criteria:

• Is currently engaged in medication treatment for OUD with methadone, BUP, or naltrexone
• Has a urine toxicology test that is positive for methadone or buprenorphine
• Currently requires prescribed opioids for treatment of an ongoing pain condition
• Has a known allergy to BUP
• Is pregnant as determined by urine hCG testing at the index ED visit
• Is breastfeeding as determined by self-report
• Has medical, psychiatric, or concurrent substance use conditions or severe cognitive impairment which might prelude safe participation
• Is a prisoner or in police custody at the time of the index ED visit
• Has previously enrolled in the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BUP treatment arm; Subjects will be given BUP 32mg in 2 doses, and observed for at least 90 minutes after the 2nd dose. The whole process will take a total of about 3-4 hours including the consenting process. Subjects will be asked questions and be examined repeatedly. Subjects will have 4 in-person visits and a phone call in addition to review of medical records.

Drug: Buprenorphine Naloxone; Participants will receive the BUP SL 32mg in divided doses rather than all at once. If after the initial 8mg dose a participant experiences over-sedation or another adverse event that would preclude further dosing, such as an allergic reaction, the subsequent dose will not be administered and the patient will be withdrawn from the study. The participant will be reassessed for other possible etiologies for these symptoms.; Other Names: Suboxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Successful Rapid Induction	This will be measured by the proportion of participants who report Successful Rapid Induction. Participants will receive a loading dose of BUP SL 32mg in the ED without experiencing a clinically significant serious and/or severe adverse event (AE) related to the intervention - specifically, the receipt of a dose of BUP SL greater than 8mg during the Index ED visit. Successful rapid induction is defined only by the outcome of the participant's visit, and not by any following research visits.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Withdrawal at Conclusion of Index Visit as Measured by the Clinical Opiate Withdrawal Scale (COWS)	The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. The tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of withdrawal and monitor these symptoms over time. The summed score can be used to help clinicians determine the stage or severity of withdrawal and assess the level of physical dependence on opioids. The total score ranges from 0 to 48. The interpretation of scores is as follows: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.	Index ED Visit 1(Day 0)
Number of Participants With Withdrawal Suppresion at Day 1 (24 Hours)	Participants who had suppression of opioid withdrawal within 24 hours of receipt of buprenorphine at the index visit as measured by having none of the following: 1) having a COWS score of >7 at the Day 1 research visit, 2) having objective signs of opioid withdrawal as assessed by a medical clinician, or 3) participant self-report of opioid use to treat opioid withdrawal.	Day 1 (24 hours)
Number of Participants With Withdrawal Suppresion by Day 2	Participants who had suppression of opioid withdrawal within 48 hours of receipt of buprenorphine at the index visit as measured by having none of the following: 1) having a COWS score of >7 at the Day 1 research visit, 2) having objective signs of opioid withdrawal as assessed by a medical clinician, or 3) participant self-report of opioid use to treat opioid withdrawal.	Day 2
Number of Participants With Withdrawal Suppression on Day 3	Participants who had suppression of opioid withdrawal within 72 hours of receipt of buprenorphine at the index visit as measured by having none of the following: 1) having a COWS score of >7 at the Day 1 research visit, 2) having objective signs of opioid withdrawal as assessed by a medical clinician, or 3) participant self-report of opioid use to treat opioid withdrawal.	Day 3

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Emergency Medicine Foundation
• Investigators: Principal Investigator: Ryan McCormack, MD, NYU Langone

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): February 25, 2023
• Study Completion (Actual): February 25, 2023

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 24, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease Attributes; Narcotic-Related Disorders; Emergencies; 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; Naloxone; Buprenorphine, Naloxone Drug Combination
• Other Study ID Numbers: 19-01700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data. Upon reasonable request. Requests should be directed to Ryan.McCormack@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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