Protocol for Take home naloxone In Multicentre Emergency setting (TIME): Feasibility Study
Authors: Jones Matthew , Bell Fiona , Benger Jonathan , Black Sarah , Buykx Penny , Dixon Simon , Driscoll Tim , Evans Bridie , Edwards Adrian , Fuller Gordon , Goodacre Steve , Hoskins Rebecca , Hughes Jane , John Ann , Jones Jenna , Moore Chris , Sampson Fiona , Watkins Alan , Snooks Helen 
Published: January 2020

Abstract
Background Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the UK are at record levels. Naloxone is an opioid antagonist which can be distributed in ‘kits’ for administration by witnesses in an overdose emergency. This intervention is known as Take Home Naloxone (THN). There is a lack of rigorous experimental research into the effectiveness of THN distribution, with fundamental questions remaining unanswered: do THN kits reduce deaths? are there unforeseen harms associated with THN distribution? and is THN distribution cost-effective? We seek to establish the feasibility of a fully-powered cluster Randomised Controlled Trial (RCT) of THN distribution in emergency settings to answer these questions.Methods We will carry out a feasibility study for a RCT of THN distributed in emergency settings at four sites, clustered by Emergency Department (ED) and catchment area within its associated ambulance service. At two intervention sites, emergency ambulance paramedics and ED clinical staff will distribute THN to adult patients who are at risk of opioid overdose. At two control sites practice will carry on as usual. THN is a peer-administered intervention. We will develop a method of identifying a population to include in an evaluation, comprising people at risk of opioid overdose, who may potentially receive THN. We will gather anonymised outcomes up to one year following a 12 month ‘live’ trial period for patients at risk of death from opioid poisoning. We expect approximately 100 patients at risk of opioid overdose to be in contact with each service during the one year recruitment period. Our outcomes will include: deaths; emergency admissions; intensive care admissions; and ED attendances. We will collect numbers of eligible patients attended by participating emergency ambulance paramedics and attending ED; THN kits issued; and NHS resource usage. We will determine whether to progress to a fully powered trial based on pre-specified progression criteria: sign-up of sites (n = 4); staff trained (>= 50%); eligible participants identified (>= 50%); THN provided to eligible participants (>= 50%); people at risk of death from opioid overdose identified for inclusion in follow up (>= 75% of overdose deaths); outcomes retrieved for high risk individuals (>= 75%); and adverse event rate (<10% difference between trial arms).Discussion This feasibility study is the first randomised, methodologically robust investigation of THN distribution in emergency settings. The study addresses an evidence gap related to the effectiveness of THN distribution in emergency settings. As this study is being carried out in emergency settings, obtaining informed consent on behalf of participants is not feasible. We therefore employ novel methods for identifying participants and capturing follow up data, the effectiveness of which are dependent on the quality of the available routine data.