Randomised trial of take-home Naloxone to prevent heroin overdose deaths post-prison release. 

Heroin-related deaths account for around 8% of all UK deaths in individuals aged 15-44.  For UK prisoners, the risk of a drugs-related death is 7.5 times higher in the first fortnight after their release than at comparable other times at liberty. Indeed, one in 200 released prisoners, with a history of heroin injection, dies from a drugs-related death within four weeks of leaving prison. Nearly all these overdose deaths are potentially preventable. However, existing prevention approaches have not adequately resolved the high risk of overdose death soon after release from prison or other settings where drug tolerance may be reduced. In Scotland, for example, drugs-related deaths occurring within four weeks of release from prison remained at around 13% between 2002 and 2005, despite Scottish Prison Service’s adoption of methadone maintenance. 

The N-ALIVE project (NALoxone InVEstigation) has two stages: The Pilot randomized trial (n=5,600) and the subsequent main randomised trial. Ultimately a total of 56,000 participants are planned to be recruited in total. The N-ALIVE trial is a large prison-based randomized controlled trial, designed to test the effectiveness of giving naloxone-on-release to prisoners with history of heroin use to prevent fatal opiate overdoses. Naloxone is an opiate antagonist commonly used to reverse the effects of a heroin overdose. 

The Pilot trial is aimed to demonstrate feasibility by recruiting the first 10% of participants (5,600 participants). The Main N-ALIVE trial will assess the number of lives that could be saved by routine provision of naloxone-on-release to adult prisoners aged 18-44 years with a history of heroin injection who are released after seven or more days in prison (whether post-detoxification, on maintenance treatment, or otherwise). The Pilot trial includes an ancillary study in which the participants who give their additional consent will be contacted once by phone. This sub-study will allow collection of additional qualitative information on opiate use, overdoses, and naloxone use soon after release. 

Eligible prisoners who give informed consent will be randomized to receive, on release from custody, either a pack containing a single ‘rescue’ injection of naloxone or a control pack containing no naloxone. The trial is ‘double-blind’ prior to the participant’s release so that neither the participant nor prison staff will know the allocation until the participant opens his/her assigned pack after release. 

What are the principal questions to be addressed? 

Pilot trial: What happens to the naloxone and the participants, in terms of heroin use and overdoses (witnessed or experienced) within 4 to 12 weeks after release? Do 75% of prisoners assigned to naloxone carry it with them in the first four weeks after release? Do prisons and prisoners participate in the numbers expected and required for the main trial? Do the N-ALIVE procedures work well logistically in the National Offender Management Service, or will they need to be changed for the main trial? If changes are necessary, what needs to be done? 

Main trial: Does giving naloxone on release to prisoners with a history of heroin injection reduce heroin overdose deaths by 28% in the first 12 weeks after release? 

Why do the Pilot and Main trials need to be randomized? 

The N-ALIVE Pilot and Main trials have to be randomized for the following reasons. First, take-home naloxone is not currently issued by UK prisons, nor by any prisons internationally. Thus, a prison-based observational study is currently not possible. If some prisons were to prescribe take-home naloxone in an uncontrolled way to observe outcomes, we would not be piloting N-ALIVE’s intervention which has been specifically designed to cleave to prison procedures and to disseminate information about emergency naloxone to prisoner-peers (whether randomized or not) and needs prison-based staff specifically for N-ALIVE – as per any well-delivered intervention for prisoners (e.g. hepatitis B immunization; methadone maintenance). After undertaking such an observational study, it would be very difficult to ‘row back’ and undertake a later randomized trial.  

Second, the risks for ex-prisoners are unknown (even by them). We cannot anticipate how availability of naloxone-on-release might alter the riskiness of their heroin use behaviour and thus there is the possibility that providing naloxone in this way may do more harm than good. We shall only be able to clearly assess this through a randomized trial. Third, there is also the possibility that providing naloxone in this way has no effect because either the individual does not carry the naloxone with them or, when needed, the naloxone is not used or not appropriately used. Fourth, the N-ALIVE awareness/information video is a prison-wide backdrop, which aims to reach all prisoners attending the prison’s induction session on drug awareness – not only to inform them about N-ALIVE but so that, as peers, they know about, and how to use, emergency naloxone, and also to understand why it is necessary to randomize.  

Fifth, prisoners realise better than anyone that, for prisons to improve (health) services to prisoners, effectiveness must be beyond question for the public to be persuaded – and that requires randomization. Sixth, we are dealing with a ‘captive population’, and thus prison-based research must cleave to the highest ethical and scientific standards, which means randomization of individuals and the need for prevention policies to demonstrate cost-effectiveness. Finally, for context on costs, less than £1.60 per day is spent on a prisoner’s food. Thus, UK prisons are hard-pressed, but they can, and have, delivered unimpeachable high-quality research evidence using now-internationally recognised ‘inside methodologies’, because they were properly supported to do so. 

Where will the N-ALIVE Pilot and Main Trials be conducted? 

Both the N-ALIVE pilot and main trials will be conducted in approximately 14 prisons in England and Wales, under the National Offender Management Service.