{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:43:40Z","timestamp":1789879420266,"version":"4.0.1"},"reference-count":21,"publisher":"National Institute for Health and Care Research","issue":"3","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["10\/46\/01"],"award-info":[{"award-number":["10\/46\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>People recovering from heroin addiction need better treatments than are currently offered. The chronic relapsing nature of drug dependence means that helping a patient to achieve abstinence is often difficult. Naltrexone blocks the effects of ingested heroin; however, evidence is conflicting regarding the best delivery method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The primary purpose of the trial was to evaluate the clinical effectiveness and cost-effectiveness of extended-release naltrexone versus standard oral naltrexone versus relapse prevention therapy without medication for opioid use disorder (OUD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>This was a 3-year, definitive, three-centre, three-arm, parallel group, placebo-controlled, double-blind, double-dummy, randomised controlled trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Two specialist NHS outpatient addiction clinics: one in London and one in Birmingham.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Planned study sample \u2013 300 adult patients with OUD who had completed detoxification.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>One iGen\/Atral-Cipan Extended Release Naltrexone device (iGen\/Atral-Cipan, Castanheira do Ribatejo, Portugal) (765\u2009mg naltrexone or placebo) at day 0 of study week 1. Three weekly directly observed active or placebo oral naltrexone tablets (2\u2009\u00d7\u200950\u2009mg, Monday and Wednesday; 3\u2009\u00d7\u200950\u2009mg, Friday) at day 0 of study week 1 (for 4 weeks) and then an 8-week regimen of patient-administered dosing at the same dosing level.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Main outcome measure<\/jats:title>\n                  <jats:p>The primary outcome measure was the proportion of heroin-negative urine drug screen (UDS) results at the end of the 12-week post-randomisation time point.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Six patients were recruited and randomised to receive study interventions. Two patients had no positive UDS samples for heroin during the 12-week treatment period, one patient had only one positive UDS sample and the remaining patients had two, six and eight positive UDS results for heroin. All patients had at least one missed clinic visit (range 1\u201314).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Considerable problems were encountered with (1) the stipulated requirement of a validated \u2018detoxified\u2019 status prior to the initiation of the study naltrexone, (2) the requirement for a consent cooling-off period and (3) delays awaiting the surgical implant procedure. Major upheaval to the organisation and delivery of NHS community treatment services across England led to extremely poor levels of actual entry of patients into the trial. Research-vital clinical and procedural requirements were, therefore, more challenging to implement. The potential therapeutic value of the opioid antagonist naltrexone still needs clear investigation, including comparison of the established oral form with the new ultra-long-acting depot implant formulations (for which no licensed products exist in Europe). Despite the small number of study participants, some tentative conclusions can be reached, relevant to potential future work. The blinding of the active\/placebo medications appeared to be good. Self-report was not sufficient to detect instances of heroin use. Self-report plus UDS information provided a fuller picture. Instances of lapsed heroin use were not necessarily followed by full relapse, and future work should consider the lapse\u2013relapse relationship. The prison release setting also warrants special consideration. In future, investigators should consider seeking ethics approval for studies in which clinical procedures to accelerate the treatment process are permitted, even if outside orthodox clinical practice, if they address a clinical need at the time of challenge and clinical risk. In addition, it may be appropriate to seek exemption from the ordinary requirement of a cooling-off period after securing consent because it is often essential to initiate treatment promptly.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>Current Controlled Trials ISRCTN95809946.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 23, No. 3. See the NIHR Journals Library website for further project information.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/hta23030","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T11:32:09Z","timestamp":1548934329000},"page":"1-72","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Extended-release naltrexone versus standard oral naltrexone versus placebo for opioid use disorder: the NEAT three-arm RCT"],"prefix":"10.3310","volume":"23","clinical-trial-number":[{"clinical-trial-number":"isrctn95809946","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-2725","authenticated-orcid":true,"given":"John","family":"Strang","sequence":"first","affiliation":[{"name":"National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London, 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