Clinical Outcomes From Nalmefene

Study Overview
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Brief Summary
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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.

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

Conditions
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Opioid Overdose

Intervention / Treatment
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* Drug: Nalmefene Hydrochloride Injection
* Drug: Naloxone Hydrochloride Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presumed or known opioid overdose in community settings. Experiencing clinically significant respiratory depression based on appropriate medical judgement. Patient airway is open and unobstructed at the time of enrollment. (Utilization of oral pharyngeal or nasal pharyngeal airway is allowed.) Pre-hospital naloxone administration is allowed. Exclusion Criteria: Patient age known or estimated to be less than 18 years. 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. Cardiac arrest, secondary to opioid intoxication. Arrested, jailed, or imprisoned patients. Inappropriate for the study per judgement of research team.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nalmefene<br>Nalmefene hydrochloride (HCl) injection | Drug: Nalmefene Hydrochloride Injection<br>* for intravenous/intramuscular/subcutaneous (IV/IM/SC) administration<br>|
| Active Comparator: Naloxone<br>Naloxone hydrochloride (HCl) injection | Drug: Naloxone Hydrochloride Injection<br>* for intravenous/intramuscular/subcutaneous (IV/IM/SC) administration<br>* Other names: Narcan;|

What is the study measuring?
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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 frequency Cumulative 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 |