Clinical Outcomes From Nalmefene (COINED)

Clinical Outcomes From Injectable Nalmefene in the Emergency Department (COINED)

The purpose of this study is to assess the effectiveness of nalmefene relative to naloxone for the reversal of opioid intoxication in emergency department (ED) settings.

Study Overview

• Status: Withdrawn
• Conditions: Opioid Overdose
• Intervention / Treatment: Drug: Nalmefene Hydrochloride Injection; Drug: Naloxone Hydrochloride Injection

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Presumed or known opioid overdose in community settings.
2. Experiencing clinically significant respiratory depression based on appropriate medical judgement.
3. Patient airway is open and unobstructed at the time of enrollment. (Utilization of oral pharyngeal or nasal pharyngeal airway is allowed.)
4. Pre-hospital naloxone administration is allowed.

Exclusion Criteria:

1. Patient age known or estimated to be less than 18 years.
2. Patient has one or more additional documented acute medical, traumatic, toxicologic, or psychiatric conditions that would extend length of treatment or adversely alter the clinical outcome.
3. Cardiac arrest, secondary to opioid intoxication.
4. Arrested, jailed, or imprisoned patients.
5. Inappropriate for the study per judgement of research team.

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: Nalmefene; Nalmefene hydrochloride (HCl) injection	Drug: Nalmefene Hydrochloride Injection; for intravenous/intramuscular/subcutaneous (IV/IM/SC) administration
Active Comparator: Naloxone; Naloxone hydrochloride (HCl) injection	Drug: Naloxone Hydrochloride Injection; for intravenous/intramuscular/subcutaneous (IV/IM/SC) administration; Other Names: Narcan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversal of Respiratory Depression	Normalization of the end tidal carbon dioxide value (if measured) to between 35 and 45 mmHg and/or ≥5 breaths per minute increase in respiratory rate from baseline (pre-dose) measurement, with rate of at least 12 breaths per minute.	Up to 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reversal from administration of opioid antagonist		Up to 3 hours
Recurrence of Respiratory Depression	Increased end tidal carbon dioxide value (if measured) above 45 mmHg when previously within the normal range and/or ≥5 breaths per minute decrease in respiratory rate from maximum post-reversal measurement, with a rate of at most 12 breaths per minute.	Up to 3 hours
ED Disposition	One of the following will apply: ED Discharge; Hospital Admission; ICU Admission; Left against medical advice; Transfer to another facility; Death.	Up to 3 hours
Drug Dosing	Dose administered for each opioid antagonist given to patients during their ED encounter -Individual dose amount and frequencyCumulative dose; Any pre-hospital naloxone given prior to ED arrival -Dose amount, route	Up to 3 hours
Richmond-Agitation Sedation Scale (RASS) Score	This is a single-item instrument used to quickly assess the degree of patient alertness and agitation in emergency and critical care settings. It is an observational assessment conducted by healthcare providers, and it can be completed in seconds. The scale uses integers from -5 to +4, each with its own clear anchor. A score of 0 means that the patient is alert and calm. Negative integers indicate diminished responsiveness and consciousness, with -1 indicating that a patient will open their eyes or make eye contact for 10 or more seconds when awakened by voice, and -5 meaning that the patient is unarousable by voice or physical stimulation. Positive integers indicate an increased level of arousal or agitation. The positive end of the scale spans from +1 (anxious, apprehensive, but not aggressive) to +4 (combative, violent, danger to staff).	Up to 3 hours
Clinical Opioid Withdrawal Scale (COWS) Score	This is an observational assessment performed by a clinician to diagnose and assess the severity of opioid withdrawal symptoms. Eleven different opioid withdrawal symptoms are included in the COWS. The clinician will score the presence and severity of each symptom, with 0 indicating that the symptom is absent and more severe symptoms warranting a higher score. Individual symptom scores are then added to determine the overall severity of the patient's withdrawal. Total scores range from 5 to 48 where 5 - 12 = mild; 13 - 24 = moderate; 25 - 36 moderately severe; and greater than 36 = severe withdrawal.	Up to 3 hours
Oxygen saturation level	Pulse oximetry monitoring will be used to assess the patient's oxygen saturation level (SpO2), expressed as a percentage from 0 to 100.	Up to 3 hours
Length of time during ED encounter	Defined as the difference between time at Triage to time at ED Disposition	Up to 3 hours

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Drug Overdose; Opiate Overdose; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone; Nalmefene
• Other Study ID Numbers: NAL4001

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