N-ALIVE: Randomised Trial of Naloxone-On-Release to Prevent Heroin Overdose Deaths on Prison Release in England

Transcription

1 N-ALIVE: Randomised Trial of Naloxone-On-Release to Prevent Heroin Overdose Deaths on Prison Release in England Professor John Strang National Addiction Centre, London, UK (on behalf of co-investigators and the N-ALIVE trial team) N-ALIVE Chief Investigators John Strang, Mahesh Parmar, Sheila Bird N-ALIVE CTU Trial Team Angela Meade and many crucial others Funding and support: MRC & research support from Mental Health Research Network

2 Declaration (personal & institutional) The university (King s College London) has registered intellectual property on a naloxone initiative, and JS has been named in a patent registration by a Pharma company as inventor of a potential novel overdose resuscitation product. DH, NTA, Home Office, NACD, EMCDDA, WHO, UNODC, NIDA. NHS provider (community & in-patient); also Phoenix House, Lifeline, Clouds House, KCA (Kent Council on Addictions). Work with pharmaceutical companies re actual or potential devrelopment of new medicines for use in the addiction treatment field (incl re naloxone products), including (past 3 years) Martindale, Reckitt-Benckiser, UCB, Napp/MundiPharma, Viropharma (Auralis), Schering-Plough, Lundbeck, Alkermes, Teva, igen and also discussions with Lightlake, Lanacher, Rusan, Fidelity International and Titan. UKDPC (UK Drug Policy Commission), SSA (Society for the Study of Addiction); and two Masters degrees (taught MSc and IPAS) and an Addictions MOOC. Work also with several charities (and received support) including Action on Addiction, and also with J Paul Getty Charitable Trust (JPGT) and Pilgrim Trust.

3 Acknowledgements All participants and those who participated in the trial N-ALIVE workers, Principal Investigators and all staff involved at each of our prisons N-ALIVE trial team: Trial Monitoring Group and Trial Steering & Data Monitoring Committee Mental Health Research Network teams

4 Reason for interest We know when it happens; we have treatment During methadone early treatment Post-detox/rehab Prison release

5 Deaths in the first few weeks post-release 45 Excess mortality ratio Not drug-related Drug-related deaths 0 Up to 1 1 up to 2 2 up to 4 4 up to 8 8 up to up to up to 52 >=52 Total Time since release (weeks) Singleton et al, Home Office report, 2002

6 Merrall et al, meta-analysis, Addiction, 2010

7 N-ALIVE trial pilot & main phase About 30% of prisoners have previously used heroin. One in 200 prisoners with history of heroin use by injection dies from a drugs-related death (DRD) within 2 4 weeks of leaving prison. Prison-release randomised trial: pilot recently concluded (n= 1,685; Dec 2014) Main study planned to be n=30,000 (15k + 15k) Large randomised trial to test effectiveness of Naloxone-onrelease to prevent deaths from overdose post-release.

8 N-ALIVE Outcome Measures Primary: Drug-Related Deaths (DRDs) within 12 weeks of the prisoner s N-ALIVE release date Secondary: DRDs within 4 weeks of the prisoner s N-ALIVE release date Non-Fatal Overdose Admissions to Accident & Emergency within the first 12 weeks after release

9 Trial Design Up to 3 months prerelease Consent & Randomisation (prisoners incarcerated >7 days, & randomised <3 months prior to release date) Naloxone Group 1:1 Control Group Prison release date Prisoner s N-ALIVE Release Date Prisoner given pack on release from custody Optional: Once-only Phone Contact in either weeks 1-2 or 3-4 post-release. Ratio: 2:1:1 Pre-paid Anonymised N-ALIVE Reply Card: re critical events 12 weeks postrelease Up to 6 months after prisoner s N-ALIVE release date 12 Weeks Post-Release National Death Record Review Retrospective prisoner consented A&E database linkage Returned Prisoner Self-Questionnaire - completed next time in prison

10 Trial Design Consent & Randomisation (prisoners incarcerated >7 days, & randomised <3 months prior to release date) Up to 3 months prerelease Naloxone Group 1:1 Control Group Prison release date Prisoner s N-ALIVE Release Date Prisoner given pack on release from custody Optional: Once-only Phone Contact in either weeks 1-2 or 3-4 post-release. Ratio: 2:1:1 Pre-paid Anonymised N-ALIVE Reply Card: re critical events Weeks Post-Release weeks postrelease National Death Record Review Retrospective prisoner consented A&E database linkage Up to 6 months after prisoner s N-ALIVE release date Returned Prisoner Self-Questionnaire - completed next time in prison

11 Trial Design Consent & Randomisation (prisoners incarcerated >7 days, & randomised <3 months prior to release date) Up to 3 months prerelease Naloxone Group 1:1 Control Group Prison release date Prisoner s N-ALIVE Release Date Prisoner given pack on release from custody Optional: Once-only Phone Contact in either weeks 1-2 or 3-4 post-release. Ratio: 2:1:1 Pre-paid Anonymised N-ALIVE Reply Card: re critical events 12 weeks postrelease 12 Weeks Post-Release National Death Record Review Retrospective prisoner consented A&E database linkage Up to 6 months after prisoner s N-ALIVE release date Returned Prisoner Self-Questionnaire - completed next time in prison

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13 Pre-filled syringe 1 mg per ml, 2 ml syringe

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15 N-ALIVE Milestones First site opened HMP Nottingham opened on 28 th May 2012 First participant randomised HMP Nottingham randomised first 3 participants on 29 th May 2012 Pilot trial in full operation 16 prisons participated; n=1685 prison-releasees Pilot trial concluded Internal review; naloxone use on other >> self; conclusion - wrong primary outcome; pilot finished on 8 th December 2014

16 N-ALIVE - embargoed preliminary analyses - not to be quoted without explicit permission of the investigators

17 N-ALIVE embargoed preliminary analyses CONSORT elements conclusions on feasibility (1) DID THE PROCESS OF RANDOMISATION WORK OK? Assessed for eligibility n=2355 Randomised n=1685 (then 9 removed) Study population n=1676 (naloxone 842; control 843) Already released by Dec 2014 n=1533 (91% of the 1676) (primary analysis population) N.B. c90% released <3/12; c95% <6/12

18 N-ALIVE embargoed preliminary analyses CONSORT elements conclusions on feasibility (2) DID THE NALOXONE-ON-RELEASE PROCESS WORK? More than 80% were released with their N-ALIVE pack Works best when pre-placed in possessions Worse with remand vs sentenced releasees Often fails if prisoner is moved between prisons

19 N-ALIVE embargoed preliminary analyses Returned Prisoner!nonymous Questionnaire TOLD FAMILY? CARRIED NALOXONE? USED NALOXONE? *** Data to follow through publications from the N-ALIVE group *** xxx% told family or friend xxx% carried naloxone with them Had used the naloxone? xxx% of naloxone recipients Self/other = xxx

20 N-ALIVE embargoed preliminary analyses Returned Prisoner!nonymous Questionnaire RAPID HEROIN USE ON RELEASE? OVERDOSE? HOSPITAL? *** Data to follow through publications from the N-ALIVE group *** Heroin use in first 2/52 post-release Heroin use (any route)? Heroin use (inject)? Heroin use (inject alone)? Overdose < 2/52? O/D victim to hospital? Naloxone group (n=112) To follow To follow To follow Control group (n=93)

21 Conclusions Equipoise windows of time of policy and practice equipoise. Prison establishments and prisoners themselves cooperative. Prison recruitment feasible; randomisation at release feasible. Follow-up post-release pathology florid (heroin use; O/D; nalox). Iatrogenic harm (nx vs control)? No. Lives saved mostly saving others, not the index case. Need to stop the N-ALIVE trial (completely; or maybe revise design).

22 Thank you

23 N-ALIVE trial YouTube clips Three trigger videos on Youtube (i) explanation of the trial (ii) how to put your naloxone kit together and give the injection (iii) how to manage an overdosehttps://