Nalmefene vs Naloxone for the Treatment of Recurrent Respiratory Depression After Opioid Overdose

NCT06408714 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: UNM24-157
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare naloxone to nalmefene for the treatment of opioid overdose in adults. The main questions it aims to answer are:

• Does nalmefene lower the number of doses of medicine participants need to treat opioid overdose?
• When participants are given nalmefene instead of naloxone, do they have fewer complications of opioid overdose such as being admitted to the hospital or having a breathing tube inserted? Researchers will compare nalmefene to naloxone for the treatment of opioid overdose. Nalmefene and naloxone are both approved medicines to treat opioid overdose. Participants who are brought to the emergency department after an opioid overdose will be given a dose of either nalmefene or naloxone if their breathing slows down again after an opioid overdose. Participants will:
• Stay in the emergency department for 8 hours after receiving a dose of nalmefene or naloxone.
• Receive a phone call 7 days after their emergency department to check on how they are doing. Background information: Naloxone (also known as Narcan) and nalmefene are opioid blocking medicines. When someone overdoses on an opioid, such as heroin or fentanyl, their breathing slows down or stops and they can die. By giving naloxone or nalmefene, the effect of the opioid can be blocked and the person can start breathing again. Naloxone is the most commonly used medicine to reverse an opioid overdose. The effect of naloxone lasts about an hour, and patients may need more than one dose of naloxone to keep them breathing. Sometimes patients overdose, get a dose of naloxone and wake up, and then some time later their breathing slows down again and they need another dose of naloxone. This can happen because the effect of the opioid they took lasts longer than the effect of the naloxone. The effect of nalmefene lasts longer than naloxone, about four hours. If a person gets nalmefene, their opioid may wear off before the nalmefene wears off and they might not need any more doses of a reversal medicine. Both naloxone and nalmefene are approved medicines for treating opioid overdose. Often, when a person overdoses on an opioid, someone gives them naloxone right away and then they are brought to the emergency department. In the emergency department, they are watched for several hours to make sure they don't stop breathing again when their naloxone wears off. If they do stop breathing again, they are given another dose of naloxone. In this study, participants will be given either nalmefene or naloxone if their breathing slows down while they are in the emergency department.

Conditions

Opioid Overdose; Opiate Overdose

Keywords

opioid overdose; opiate overdose; drug overdose; naloxone; nalmefene; respiratory depression

Outcome Measures

Primary Outcomes (1)

• Recurrent respiratory depression

  Recurrent respiratory depression requiring repeat treatment with an opioid antagonist. Respiratory depression is defined as a respiratory rate (RR) \<8 breaths per minute or end-tidal CO2 (ETCO2)\> 50 mm Hg.

  Within 8 hours of intervention

Secondary Outcomes (2)

• Precipitated withdrawal

  Within 8 hours of intervention

• Serious adverse event

  Within 8 hours of intervention

Study Arms (2)

Nalmefene

EXPERIMENTAL

Nalmefene Rescue Study Arm Treatment: Subjects will receive study drug if they exhibit respiratory depression (defined as respiratory rate less than 8 breaths per minute and/or end-tidal carbon dioxide measurement of greater than 50 mm Hg) lasting for longer than 10 seconds. Respiratory support with bag-valve mask and/or supplemental oxygen will be provided while the study drug is being prepared. Nalmefene will be administered as per intervention description.

Drug: Nalmefene Injection

Naloxone

ACTIVE COMPARATOR

Naloxone Rescue Arm Treatment: Subjects will receive study drug if they exhibit respiratory depression (defined as respiratory rate less than 8 breaths per minute and/or end-tidal carbon dioxide measurement of greater than 50 mm Hg) lasting for longer than 10 seconds. Respiratory support with bag-valve mask and/or supplemental oxygen will be provided while the study drug is being prepared. Naloxone will be administered as per intervention description.

Drug: Naloxone Injection

Interventions

Nalmefene Injection DRUG

Subjects in this arm will be administered intravenous nalmefene with a dosing scheme of: 0.5 mg Nalmefene IV If an adequate response (increase in RR of at least 5 breaths per minute and minimum respiratory rate of 12 breaths per minute or reduction in ETCO2 to 40 mm Hg) is not attained after 2 minutes, an additional 1.0 mg nalmefene will be administered. If an adequate response is not attained after an additional 2 minutes of observation, naloxone may be administered as a rescue agent at the treating physician's discretion.

Also known as: Nalmefene, Nalmefene hydrochloride, Nalmefene HCl

Nalmefene

Naloxone Injection DRUG

Subjects in this arm will be administered intravenous naloxone with a dosing scheme of: 0.4 mg Naloxone IV If an adequate response (increase in RR of at least 5 breaths per minute and minimum respiratory rate of 12 breaths per minute or reduction in ETCO2 to 40 mm Hg) is not attained after 2 minutes, an additional 0.4 mg of naloxone will be administered. If an adequate response is not attained after an additional 2 minutes of observation, naloxone may be administered as a rescue agent at the treating physician's discretion.

Also known as: Naloxone, Naloxone HCl, Naloxone hydrochloride

Naloxone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (age ≥ 18 years) presenting to the UNM ED after a suspected acute opioid overdose event requiring at least one dose of naloxone.

You may not qualify if:

• age \<18 years
• non-English speaking
• unable to or unwilling to provide consent to research participation
• allergy to naloxone
• allergy to nalmefene
• inability to establish IV access
• prior enrollment in the current study
• no working phone number for follow-up contact
• buprenorphine administration during the ED visit prior to enrollment.
• known pregnancy at the time of enrollment

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87106, United States

Location

Related Publications (3)

• Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998 Apr 30;17(8):873-90. doi: 10.1002/(sici)1097-0258(19980430)17:83.0.co;2-i.

  PMID: 9595617 BACKGROUND

• Wei LJ, Lin DY, Weissfeld L. Regression analysis of multivariate incomplete failure time data by modeling marginal distributions. J Am Stat Assoc. 1989;84:1065-1073.

  BACKGROUND

• McLaughlin SA, Crandall CS, McKinney PE. Octreotide: an antidote for sulfonylurea-induced hypoglycemia. Ann Emerg Med. 2000 Aug;36(2):133-138. doi: 10.1067/mem.2000.108183.

  PMID: 10918104 BACKGROUND

MeSH Terms

Conditions

Opiate Overdose; Drug Overdose; Respiratory Insufficiency

Interventions

nalmefene; Naloxone

Condition Hierarchy (Ancestors)

Prescription Drug Misuse; Drug Misuse; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Narcotic-Related Disorders; Mental Disorders; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Caitlin Bonney, MD

  University of New Mexico Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Emergency Medicine

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 10, 2024
• Study Start: August 26, 2024
• Primary Completion: December 9, 2024
• Study Completion: December 9, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)