Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial

Abstract

Introduction and aims: Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin use by injection have a high risk of drug-related death in the first weeks after prison-release. The N-ALIVE trial was planned as a large prison-based randomised controlled trial (RCT) to test the effectiveness of naloxone-on-release in the prevention of fatal opiate overdoses soon after release. The N-ALIVE pilot trial was conducted to test the main trial's assumptions on recruitment of prisons and prisoners, and the logistics for ensuring that participants received their N-ALIVE pack on release.

Design and methods: Adult prisoners who had ever injected heroin, were incarcerated for ≥7 days and were expected to be released within 3 months were eligible. Participants were randomised to receive, on liberation, a pack containing a single 'rescue' injection of naloxone or a control pack with no naloxone syringe. The trial was double-blind prior to prison-release.

Results: We randomised 1685 prisoners (842 naloxone; 843 control) across 16 prisons in England. We stopped randomisation on 8 December 2014 because only one-third of administrations of naloxone-on-release were to the randomised ex-prisoner; two-thirds were to others whom we were not tracing.

Discussion and conclusions: Prevention RCTs are seldom conducted within prisons; we demonstrated the feasibility of conducting a multi-prison RCT to prevent fatality from opioid overdose in the outside community. We terminated the N-ALIVE trial due to the infeasibility of individualised randomisation to naloxone-on-release. Large RCTs are feasible within prisons.

Keywords: N-ALIVE; drug-related death; naloxone; prison-release; randomised.

Figure 1

N‐ALIVE pilot trial design.

Figure 2

National and local approvals for N‐ALIVE. *If the N‐ALIVE pilot trial were being conducted today we would apply for approvals through the Health Research Authority process. HSC, Health and Social Care; NHS, National Health Service.

Figure 3

Map of N‐ALIVE prisons and the Mental Health Research Network hubs.

Figure 4

The N‐ALIVE naloxone wallet. N‐ALIVE trial wallet containing the naloxone‐filled syringe and needle, information on overdose management and ‘authorisation to carry’ card.

Figure 5

CONSORT diagram (originally published in Parmar et al. [16]). Screening records have only been kept since September 2012 so only provide a snapshot of the proportions deemed eligible and subsequently randomised. *Excluded from ITT analysis participants released after recruitment closure (n = 48, 40). **Included in PP analysis participants released with pack only.