European Cohort Study of the Effectiveness of Take Home Naloxone

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

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.

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.

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