Title: TIME: Take home naloxone Intervention Multi centre Emergency setting feasibility trial
Funder: Health and Care Research Wales (Welsh Government)

Abstract: DESIGN Randomised feasibility trial clustered by Emergency Department (ED) catchment area, with anonymised linked outcomes for trial participants and peers, aggregate outcomes at population level; qualitative methods. SETTING Emergency settings (community and ED) TARGET POPULATION Adult opioid users at risk of overdose INCLUSION CRITERIA Eligible for intervention: At the intervention sites - adult opioid users at risk of overdose 1) are attended by emergency ambulance paramedic OR 2) attend ED and accompanying friends, relatives or carers Eligible for inclusion in outcome follow up and analyses: people at high risk of death from opioid overdose, including people eligible for THN provision and a wider peer group. Criteria to be developed using analysis of linked ONS/inpatient/ED data related to opioid deaths in Wales. HTA Based on intervention we have recently tested in a feasibility study of THN provision by paramedics in Cardiff. OUTCOMES This feasibility study is to inform a decision about whether a full trial of THN in emergency settings is feasible. We will define progression criteria at the outset related to: site, staff and patient recruitment; acceptability; adherence to protocols; safety and retrieval of health outcomes. We propose to gather the following anonymised linked data outcomes up to 1 year: Deaths (and drug related) Emergency admissions ITU admissions ED attendances and 999 attendances (and for overdose) THN kits issued NHS resource usage We will assess effects at aggregate (population) level on: 999 and ED attendances for opioid overdose Drug related deaths We will assess intervention costs. Based on our current feasibility study we will not attempt to gather self-reported outcomes in this population. We will explore other methods of identifying high risk patients e.g. through drug services and will flag patients offered THN in order to assess intervention 'reach'. We will collect qualitative data by interview with patients, peers and staff, to describe barriers and facilitators to THN implementation. SAMPLE SIZE Based on preliminary analysis of our Cardiff data (recruitment and mortality rates, but no ICC estimate), we will include 4 sites (ED catchment areas) each with >= 100 opioid overdose related ED attendances annually, and select 2 intervention sites at random. This will allow us to test intervention delivery and trial methods; but not to detect plausible differences in effectiveness outcomes. Data from this feasibility study will inform design of a full clustered trial; current data indicate >=5 sites and 1675 patients per arm needed to detect a difference in mortality from 6.5% to 4%, at 90% power and 5% significance. CARE PATHWAYS Currently patients attended by 999 paramedics or at ED receive care for their condition and may be referred for further care. During the trial in the intervention areas patients will also be eligible for THN and training. PROJECT TIMETABLE Months 0-6 Permissions, set up, recruitment and training of paramedics and ED staff 7-18 Patient recruitment, qualitative data collection 19-25 Data linkage, outcome follow up 26-30 Analysis against objectives and progression criteria, full trial planning if indicated EXPERTISE Highly experienced team, specialists in emergency medicine and prehospital care, addiction psychiatry, public health, trial design, statistics, health economics, with strong PPI input

Lay abstract: People who take opioid drugs such as heroin can overdose. The number of people who die this way is increasing, which has tragic consequences for families, friends and communities. Naloxone is a drug that can reverse the effects of opioid overdose. Emergency ambulance staff and doctors in the Emergency Department regularly administer naloxone. But some people die before they reach emergency medical services. There are schemes in the UK and internationally where naloxone is given to drug users to administer to others in an emergency. This is called ‘Take Home Naloxone’ (THN). But we don’t know whether THN saves lives. There are some concerns that it could encourage risk-taking behaviour i.e. the drug user feeling that they have a “safety net” and can take a higher dose. We will carry out an initial study to see 1) whether it is possible for ambulance paramedics and Emergency Department staff to give out THN kits to drug users they see, and 2) if we can collect data about this new way of distributing naloxone to find out whether it reduces deaths from overdose. We will include people who have overdosed and drug users who present with other drug-related problems such as an abscess. Because we know that drug users may share THN kits, we are aiming to reach as many drug users as possible in our follow up. We will carry out this study in two areas where THN will be given to patients who have overdosed or who are at risk of overdose (Emergency Department and the ambulance paramedics who serve that hospital) and two other areas where THN kits are not given out. We recently carried out a study with emergency ambulances in Cardiff so we know that paramedics will give out THN and that about half of suitable patients who had recovered from an overdose accepted a kit. We found that it is very difficult to follow up these patients because they don’t respond to phone calls or may have no fixed address. Therefore, in this study we will follow what happens to patients using the routine information which health services already collect about everyone they see. We will collect information about deaths, overdoses, emergency ambulance calls and emergency department attendances and admissions up to 1 year after patients are seen. We will compare these figures between the area which gives out THN and the areas which do not. To find out about the experiences and views of patients receiving THN and staff who give out the kits, we will carry out interviews. If this feasibility study shows it is possible to give out THN kits through emergency services, and that we can collect data about effects, we will plan a larger trial of THN in emergency settings to find out whether it reduces deaths. We have talked to family members affected by drug overdose and to services which help drug users and give out THN. We have also talked to a group of NHS patients who are involved in research about emergency care. They all believe this research is needed. Two people with personal experience of THN are part of our research team alongside researchers and specialists in emergency medicine, addiction, general practice, and public health. We have consulted national specialist groups and gained support from potential sites. We will publish our results in journals read by clinicians, policy makers, service managers and researchers. We will give presentations to conferences and meetings where these groups can also discuss our findings with us.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: INJURIES AND ACCIDENTS;MENTAL HEALTH