European Cohort Study of the Effectiveness of Take Home Naloxone

Study Overview
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Brief Summary
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This study aims to assess the effectiveness of take-home naloxone (THN) to reverse opioid overdose when administered by lay persons in a real world setting. This multicentre, prospective, observational cohort study will be conducted across Europe using a mixed method approach. Recruiting 6000 individuals to whom a supply of THN has been provided, for n=600 to witness an opioid overdose. The co-primary outcomes are to determine the rate of administration of naloxone and frequency of deaths in the 24 hours subsequent to the administration of naloxone. This will be captured through structured interviews with those who report witnessing an opioid overdose in the 6 month study period, approximately n=600, to elicit further information on the overdose and any naloxone administered. Naloxone training materials and education provided will be examined through questions in the structured interview. In-depth qualitative interviews will also be conducted with 60 participants who have witnessed an overdose, in order to better understand the use, safety and effectiveness of different naloxone products (particularly Nyxoid). As part of the qualitative analysis, interview transcripts will be assessed by an expert clinician panel for accuracy of diagnosis, actions taken and aftercare. Routine data from national health registers will be used to gather mortality data. This study will report on the use of different formulations of naloxone. In addition, this study serves as a Post Authorisation Efficacy Study (PAES) for the intranasal (IN) naloxone, Nyxoid developed by MundiPharma and focuses on drug safety and training.

Detailed Description
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Accidental opioid overdose is a global crisis. Naloxone is an accessible, safe and effective antidote for this preventable cause of mortality. While it has been used to treat opioid overdose in hospital and pre-hospital settings since the 1970s, take home naloxone programmes have been introduced more recently after opioid users were recognised as potential first responders. This study aims to assess the effectiveness of take-home naloxone (THN) to reverse opioid overdose when administered by lay persons in a real world setting. This multicentre, prospective, observational cohort study will be conducted across Europe using a mixed method approach, recruiting 6000 individuals to whom a supply of THN has been provided (comprising four groups:1. patients in treatment for opioid use disorder (OUD), 2. Individuals using opioids but out-of-treatment, 3. family members, friends and other close carers, and 4. staff working with individuals with OUD) for n=600 to witness an opioid overdose. The co-primary outcomes are to determine the rate of administration of naloxone and frequency of deaths in the 24 hours subsequent to the administration of naloxone. This will be captured through two stages and two sub-studies. Main study stage 1: All consenting participants (n=6,000) will be asked to complete an enrolment questionnaire with the member of staff recruiting them into the study. In addition, the staff member will be asked to complete a brief record of the naloxone and training provided to the participant. Participants will be texted monthly to prompt them to contact research staff if they have witnessed an opioid overdose. Staff who have frequent or regular contact with participants (including instances when a replenishment of naloxone is given) will also prompt participants to make contact with research staff to notify them of a witnessed opioid overdose. All participants will be contacted at six months and asked to take part in a structured interview. In addition, national/regional death registers will be probed to confirm mortality data for study participants who are at risk of experiencing an opioid overdose themselves. Main study, Stage 2: Participants who report that they have witnessed an opioid overdose during the six-month follow-up period will be asked to take part in a structured interview with a researcher about this witnessed overdose to capture our primary outcomes (approximately n=600). Sub-study A: comprises two structured surveys incorporated into a) the Enrolment training information form (to examine naloxone training and materials provided) and b) the Stage 2 Interview completed by participants who have witnessed an overdose (to ask about the extent they followed the nasal naloxone Nyxoid Quick Start Guide (QSG) (or equivalent instructions). The questions are designed to better understand the effectiveness of the Nyxoid nasal naloxone educational and training materials delivered to participants who were provided with Nyxoid nasal naloxone and who were subsequently present at an overdose. Sub-study B: comprises qualitative interviews with 60 UK participants who witness a diverse range of overdose events of the approx. n=600 (Main Study Stage 2). The aim of sub-study B is to better understand the use, safety, and effectiveness of different naloxone products. Qualitative interviews will be guided by a topic guide and conducted by telephone. The topic guide will capture details of any overdoses experienced or witnessed since the study started before focusing in more depth on the most recent overdose witnessed. Participants will also be asked about any training they have had, or need, in naloxone administration. In addition, a clinical expert assessment of the accurate identification of an opioid overdose and the participant's response to the opioid overdose (as detailed in the transcribed interviews) will be performed and documented. Answers will be assessed by an expert clinician panel for accuracy of diagnosis, actions taken and aftercare. This study will report on the use of different formulations of naloxone, and different national systems of training and provision. In addition, this study serves as a Post Authorisation Efficacy Study (PAES) for the intranasal (IN) naloxone, Nyxoid developed by Mundipharma and focuses on drug safety and training.

Official Title
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A Multi-national, Prospective Mixed Methods Study of the Effectiveness of Naloxone (Including Intranasal Nyxoid) Administration by Lay People in Reversing Opioid Overdose

Conditions
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Opioid Overdose

Intervention / Treatment
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* Drug: Naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Member of at least one of the groups above (a-d) Aged ≥18 years Provided with THN supply at time of enrolment (or can demonstrate that they have a supply of THN (in-date) and have received training at time of enrolment). Have access to reliable mobile telephone and can present it. Willing to participate in follow-up Who have provided written informed consent. Exclusion Criteria: The following persons will be excluded: Needs an interpreter Already entered the study Not willing or able to partake in follow-up telephone survey

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| lay person provided with take home naloxone<br>Naloxone all forms | Drug: Naloxone<br>* Take Home Naloxone for reversing opioid overdose<br>* Other names: Ventizolve;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of deaths in the 24 hours or later if information is available subsequent to administration of naloxone by lay-persons to reverse an opioid overdose in the real world. | frequency of deaths among those witnessing opioid overdose (n=600) | Ongoing - over six months period post enrolment (at most recent overdose witnessed) | 
| Administration rate of THN with the intention of reversing an opioid overdose by lay persons provided with THN who witness an opioid overdose. | Rate of THN administration among those witnessing opioid overdose (n=600) | Ongoing -over six months period post enrolment (at most recent overdose witnessed) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who indicate carrying THN (on day of interview) | Percentage (n=6000) | Ongoing over 6-month period post enrolment | 
| Percentage of participants who witness an opioid overdose over 6-month period. | Percentage (n=6000) | Ongoing over 6-month period post enrolment | 
| Confirm death or survival of participants | percentage (n=600) | On-going over 6 month period post enrolment | 
| Percentage of participants who witness an opioid overdose who report there was THN present | Percentage (n=600) | Ongoing over 6-month period post enrolment (at most recent overdose witnessed) | 
| Percentage of participants who are carrying THN when witness an opioid overdose | Percentage (n=600) | Ongoing over 6-month period post enrolment (at most recent overdose witnessed) | 
| Percentage of participants who witness an opioid overdose, where there was THN present, and administer THN | Percentage (n=600) | Ongoing over 6-month period post enrolment (at most recent overdose witnessed) | 
| Percentage of participants who witness an overdose and administer THN who report respiratory depression occurred in person they resuscitated within one hour of administering THN | Percentage (n=600) | On-going within 6-month period post enrolment (at most recent overdose witnessed) | 
| Percentage of participants who witness an overdose, who report a second dose of naloxone administered to a person experiencing an opioid overdose within 1-hour post administration of first dose of THN | Percentage (n=600) | 6-month follow-up (at most recent overdose witnessed) | 
| Percentage of participants who report withdrawal symptoms (including anger, rage and violence) occurred in person they resuscitated with THN | Frequency of each symptom witnessed (n=600) (at most recent overdose witnessed) | On-going over 6-month period post enrolment (at most recent overdose witnessed) | 
| Percentage of participants witnessing an overdose where the person receiving naloxone has survived at 2 hours post administration of naloxone OR at arrival of ambulance/medical assistance if this occurs before 2 hours have passed since opioid overdose | Percentage (n=600) | Ongoing over 6-month period post enrolment | 
| Percentage of participants who witness an opioid overdose and report fatal outcomes within 2 hours of identification of opioid overdose or at arrival of ambulance/medical assistance a) of witnessed opioid overdoses b) Of witnessed opioid overdoses | Percentage (n=600) | Ongoing over 6-month period post enrolment | 
| Percentage of participants who witness an overdose who correctly diagnosed opioid overdose crisis-through multiple response questions | Percentage (n=600) | Ongoing interviews 6-month post enrolment follow-up | 
| Percentage of participants who witness an opioid overdose who correctly diagnose opioid overdose crisis-through multiple response questions | Percentage (n=600) | Ongoing interviews 6-month post enrolment follow-up | 
| Percentage of participants who witness an opioid overdose who correctly respond to opioid overdose crisis-through multiple response questions | Percentage (n=600) | Ongoing interviews 6-month post enrolment follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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overdose, take home naloxone, opioids, effectiveness, prevention, fatalities, mixed methods