A European, mixed methods, cohort study of the effectiveness of naloxone administration by laypeople, in reversing opioid overdose (NalPORS): protocol and design challenges

Background: Worldwide, opioid use causes around 100,000 overdose deaths each year. Naloxone is approved as an emergency antidote to opioid overdose. Take-home naloxone (THN) programmes have been introduced to provide ‘laypeople’, who may observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone. The acceptability and feasibility of THN programmes have been demonstrated, but the real-life effectiveness of naloxone administration by laypeople is unknown. The recent approval of concentrated naloxone nasal-spray formulations (in addition to injectable formulations) potentially increases acceptability and scope for wider provision. This study aims to determine the effectiveness of THN (all formulations) in real-world conditions.

Methods: We are undertaking a European, multi-country, prospective cohort study, to assess the use of THN by laypeople during opioid overdoses over a six-month, follow-up period. Six thousand participants, provided with THN from participating harm reduction and drug treatment sites, are being recruited and followed-up for six-months. All participants who witness an opioid overdose during the six-month period (target approx. 600) are being asked to participate in a structured interview about this event. Of these, 60 are also being invited to participate in a qualitative interview. A Post Authorisation Efficacy Study (PAES) for the concentrated nasal naloxone, Nyxoid, has been integrated into the study design.

Results: Results will be available in the autumn of 2024.

Discussion: There are challenges involved in evaluating the real-life effectiveness of THN. It is not possible to use a randomised trial design, recruitment patterns will depend upon recruitment sites distributing THN, and the type of THN received by participants will depend on regulations and on local clinical and policy decision-makers. Maintaining contact with study participants is difficult, but we are using text-message reminders and staff contact to optimise retention. To accommodate COVID-19 social distancing restrictions, all study components can be carried out remotely.