Condition category
Injury, Occupational Diseases, Poisoning
Date applied
09/02/2018
Date assigned
16/02/2018
Last edited
16/02/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
People who take opioid drugs such as heroin can overdose. The number of people who die this way is increasing, with 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 give drug users 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 give to others in an emergency. This is called ‘Take Home Naloxone’ (THN). It is not known whether THN saves lives. There are some concerns that it could encourage risk-taking behaviour, with the drug user feeling that they have a “safety net” and can take a higher dose. The aim of this study is to see whether it is possible for ambulance paramedics and Emergency Department staff to give out THN kits to drug users they see, and to see if it is possible to collect data to find out whether it reduces deaths from overdose.

Who can participate?
Adult (aged 18 or over) opioid users at risk of overdose who are attended by emergency ambulance paramedic or who attend ED, and their accompanying friends, relatives or carers

What does the study involve?
This study is carried out in two areas where THN is given to patients who have overdosed or who are at risk of overdose, and two other areas where THN kits are not given out (treatment as usual). It is very difficult to follow up these patients because they don’t respond to phone calls or may have no fixed address, therefore this study follows what happens to patients using the routine information which health services already collect about everyone they see. Information is collected about deaths, overdoses, emergency ambulance calls and emergency department attendances and admissions up to 1 year after the patients are seen. These figures are compared between the areas which give out THN and the areas which do not. Interviews are also carried out to find out about the experiences and views of patients receiving THN and staff who give out the kits.

What are the possible benefits and risks of participating?
If this study shows it is possible to give out THN kits through emergency services, and that data can be collected about the effects, a larger study will be carried out to find out whether THN reduces deaths. THN is known to have the potential to save lives on an individual basis, but on an aggregate level the benefits and harms are unknown, which is the reason for this study. There are no participant incentives on offer due to the study design.

Where is the study run from?
1. Bristol Royal Infirmary (UK)
2. Hull Royal Infirmary (UK)
3. Northern General Hospital Sheffield (UK)
4. Wrexham Maelor Hospital (UK)

When is the study starting and how long is it expected to run for?
March 2018 to November 2020

Who is funding the study?
NIHR Health Technology Assessment Programme (UK)

Who is the main contact?
Matthew Jones
m.b.jones@swansea.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Matthew Jones

ORCID ID

Contact details

Floor 2
ILS2
Swansea University
Swansea
SA2 8PP
United Kingdom
+44 (0)1792513409
m.b.jones@swansea.ac.uk

Type

Scientific

Additional contact

Prof Helen Snooks

ORCID ID

Contact details

Floor 2
ILS2
Singleton Park Campus
Swansea
SA28PP
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 16/91/04

Study information

Scientific title

Take home naloxone Intervention Multicentre Emergency setting feasibility trial

Acronym

TIME

Study hypothesis

That it is feasible to conduct a fully powered randomised controlled trial to measure the clinical and cost effectiveness of take home naloxone distributed from emergency care settings using a cluster design and linked anonymised routine data.

Ethics approval

Wales REC 3 - submission pending

Study design

Feasibility study for a randomised controlled trial

Primary study design

Interventional

Secondary study design

Cluster randomised trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Opioid overdose

Intervention

This is a feasibility study for an RCT of Take Home Naloxone (THN) in emergency settings clustered by emergency department (ED) catchment area and local ambulance service. Anonymised linked data outcomes will be captured for trial participants and their peers, and aggregate outcomes at general population level. The trialists will also collect qualitative data to examine implementation, patient safety and experience.

The four sites to be randomly allocated to study arms are:
Bristol: Bristol Royal Infirmary & associated ambulance service catchment area
Hull: Hull Royal Infirmary & associated ambulance service catchment area
Sheffield: Northern General Hospital Sheffield & associated ambulance service catchment area
Wrexham: Wrexham Maelor Hospital & associated ambulance service catchment area
It was agreed that the randomisation would be stratified to ensure that the two sites served by the Yorkshire Ambulance Service would be in different study arms; this reduced the randomisation options to four, as listed below:

Option A:
Intervention: Wrexham, Sheffield
Control: Bristol, Hull

Option B:
Intervention: Bristol, Hull
Control: Wrexham, Sheffield

Option C:
Intervention: Bristol, Sheffield
Control: Wrexham, Hull

Option D:
Intervention: Wrexham, Hull
Control: Bristol, Sheffield

Four identical opaque envelopes, each containing one option, were prepared, presented to a person not involved in their preparation, and one selected at random. The chosen envelope contained Option B, so that the proposed allocation is:
Intervention: Bristol, Hull
Control: Wrexham, Sheffield

The THN intervention will consist of training for participating paramedics and ED staff; a protocol for the supply of THN kits to those eligible for the intervention; a single use THN kit (ampoule of Naloxone Hydrochloride 400 micrograms/ml solution for intramuscular injection and syringe; and instructions on how to correctly administer the naloxone dose and provide basic life support in event of overdose). The training provided to recipients of THN kits by paramedic or ED staff will include preparation and administration of the naloxone, providing appropriate aftercare including calling 999, and resuscitation techniques. The trialists will consult with patient and public interest (PPI) representatives and a wider group of service users, addiction specialists, paramedics, and ED staff to assess acceptability, and identify advantages and disadvantages of our proposed THN kit. THN will be distributed in the intervention sites for a period of 12 months.

Control sites will operate treatment as usual (TAU).

The study will be carried out in the prehospital environment and at a receiving ED at each site. The prehospital environment will be the geographic catchment area for the receiving ED. Paramedics and clinical ED staff at study sites will be invited to take part.

The target populations eligible for the intervention (THN) will be: opioid users at high risk of fatal overdose who are attended by emergency ambulance paramedic or who attend ED; their accompanying friends, relatives or carers; and people at high risk of fatal overdose who make up a wider peer group of opioid users coming in to contact with emergency ambulance paramedics or ED.

The trialists propose to develop and test two related methods of defining these populations:
1. A discriminant function incorporating routinely recorded risk predictors used in risk indices for opioid-related events. These will be derived from linked opioid-related mortality (from ONS), ED and inpatient data. They have already obtained linked data to study the characteristics of decedents of opioid overdose in Wales during 2015, and they will extend this data set to cover those with ED and inpatient events associated with non-fatal opioid overdoses, and those with no such events. Although discriminant analysis is inherently multivariate in nature, they will also assess whether the discriminant function can be reduced to a single individual-level risk score; consider thresholds used in its definition; and evaluate its performance.
2. The discriminant analysis approach outlined will include recent ED and inpatient data related to opioid overdose and associated events, for which current coding is known to be of variable quality or low specificity. The trialists will therefore test whether the planned Emergency Care DataSet (ECDS) provides reliable data about attendances for opioid overdose and related problems that could be used to improve the ability to identify both the patients eligible for THN provision and the wider peer group.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

Mortality (total and opioid overdose related), collected using anonymised data linkage at a single time point 12 months post intervention

Secondary outcome measures

Collected using anonymised data linkage at a single time point 12 months post intervention:
1. Emergency admissions
2. ITU admissions
3. ED attendances (total and opioid overdose related)
4. 999 attendances (total and opioid overdose related)
5. THN kits issued
6. NHS resource usage

Overall trial start date

01/03/2018

Overall trial end date

01/11/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Eligible for intervention:
Adult (18 years of age or over, male or female) opioid users at risk of overdose who are attended by emergency ambulance paramedic or who attend ED

Accompanying friends, relatives or carers (18 years of age or over, male or female) of opioid users at risk of overdose who are attended by emergency ambulance paramedic or who attend ED

Eligible for inclusion in outcome follow up and analyses:
High risk peers (18 years of age or over, male or female) - opioid users at high risk of fatal opioid overdose who make up a wider peer group who may or may not make contact with emergency services at study site during the study period

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

4 clusters. Target of 200 patients actively seen by emergency services (ED or ambulance) during study period. Target of 1000 'high risk' patients to be followed up using routine anonymised linked data from each cluster.

Participant exclusion criteria

1. Under 18 years of age
2. Actively dissent from involvement in study
3. Non-opioid overdose

Recruitment start date

01/09/2018

Recruitment end date

01/09/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Yorkshire Ambulance Service
WF2 0XQ

Trial participating centre

South Western Ambulance Service Foundation Trust
EX2 7HY

Trial participating centre

Welsh Ambulance Service Trust
LL17 0RS

Trial participating centre

Northern General Hospital ED
S5 7AU

Trial participating centre

Hull Royal Infirmary ED
HU3 2JZ

Trial participating centre

Bristol Royal Infirmary ED
BS2 8HW

Trial participating centre

Wrexham Maelor ED
LL13 7TD

Sponsor information

Organisation

Swansea University

Sponsor details

Research Engagement & Innovation Services
Swansea
SA2 8PP
United Kingdom
+44 (0)1792 205678
researchgovernance@swansea.ac.uk

Sponsor type

University/education

Website

http://www.swansea.ac.uk/reis/

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The study protocol is currently out for circulation with the wider team but will be submitted for publication in a peer reviewed journal in the near future (BMC Pilot and Feasibility Studies). The trialists will publish their results in journals read by clinicians, policy makers, service managers and researchers. They will give presentations to conferences and meetings where these groups can also discuss the findings with them.

IPD sharing statement
Quantitative outcome data will be stored in the SAIL databank and accessed via the secure sail gateway (https://saildatabank.com/). Research team members (myself and Dr Alan Watkins the trial statistician) have access to the gateway via yubikey (https://www.yubico.com/). The trialists are able to access the data but cannot take data outside of the gateway. Requests for exporting linked data in to the gateway are reviewed by internal and then external reviewers prior to being granted. Data will be linked and anonymised prior to export in to the gateway by NHS Digital and NWIS (for Welsh control site).

Intention to publish date

01/09/2021

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes