{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:34:04Z","timestamp":1773203644502,"version":"3.50.1"},"reference-count":25,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CS\/14\/4\/30972"],"award-info":[{"award-number":["CS\/14\/4\/30972"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["Health and Care Research Scholarship"],"award-info":[{"award-number":["Health and Care Research Scholarship"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["Senior Investigator"],"award-info":[{"award-number":["Senior Investigator"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"publisher","award":["SA L-SMP 18\\1000"],"award-info":[{"award-number":["SA L-SMP 18\\1000"]}],"id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Stroke Vasc Neurol"],"accepted":{"date-parts":[[2022,8,12]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4\u2009hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined \u2018brain frailty\u2019 markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95%\u2009CI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS&gt;2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging \u2018brain frailty\u2019 was common: median score 2 [2, 3] (range 0\u20133). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95%\u2009CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95%\u2009CI \u22120.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1\u2009hour of symptom onset and in those with more severe stroke.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/svn-2022-001634","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T13:21:32Z","timestamp":1686230492000},"page":"38-49","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"isrctn26986053","registry":"10.18810\/isrctn"},{"clinical-trial-number":"isrctn26986053","registry":"10.18810\/isrctn"},{"clinical-trial-number":"isrctn66434824","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2604-4410","authenticated-orcid":false,"given":"Jason Philip","family":"Appleton","sequence":"first","affiliation":[{"name":"Stroke, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"},{"name":"Institute of Applied Health Research, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-1999","authenticated-orcid":false,"given":"Lisa J","family":"Woodhouse","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig S","family":"Anderson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The George Institute for Global Health, Sydney, New South Wales, Australia"},{"name":"The George Institute China at Peking University Health Science Center, Beijing, China"},{"name":"Neurology, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Ankolekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, King's College Hospital NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"Cala","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Dixon","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham, UK"},{"name":"East Midlands Ambulance Service NHS Trust, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J","family":"England","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6486-3783","authenticated-orcid":false,"given":"Kailash","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Stroke, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"Mair","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, Dementia Research Institute, Univeristy of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith W","family":"Muir","sequence":"additional","affiliation":[{"name":"Institute of Neurology and Psychology, University of Glasgow, Glasgow, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Potter","sequence":"additional","affiliation":[{"name":"Bob Champion Research and Education Building, University of East Anglia, Norwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher I","family":"Price","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Randall","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thompson G","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Roffe","sequence":"additional","affiliation":[{"name":"Stroke Research in Stoke, Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Else C","family":"Sandset","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital, Oslo, Norway"},{"name":"Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L","family":"Saver","sequence":"additional","affiliation":[{"name":"Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Shone","sequence":"additional","affiliation":[{"name":"Research and Graduate Services, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aloysius Niroshan","family":"Siriwardena","sequence":"additional","affiliation":[{"name":"East Midlands Ambulance Service NHS Trust, Nottingham, UK"},{"name":"Community and Health Research Unit, University of Lincoln, Lincoln, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-6642","authenticated-orcid":false,"given":"Joanna M","family":"Wardlaw","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, Dementia Research Institute, Univeristy of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Sprigg","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham, UK"},{"name":"Stroke, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-5132","authenticated-orcid":false,"given":"Philip M","family":"Bath","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Mental Health and Clinical Neurosciences, University of Nottingham, Nottingham, UK"},{"name":"Stroke, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"2025082410222306000_9.1.38.1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000014509.11540.66"},{"key":"2025082410222306000_9.1.38.2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000118134.56524.b1"},{"key":"2025082410222306000_9.1.38.3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.282543"},{"key":"2025082410222306000_9.1.38.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60104-9"},{"key":"2025082410222306000_9.1.38.5","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.008512"},{"key":"2025082410222306000_9.1.38.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61121-1"},{"key":"2025082410222306000_9.1.38.7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6624.737"},{"key":"2025082410222306000_9.1.38.8","doi-asserted-by":"publisher","DOI":"10.1159\/000107324"},{"key":"2025082410222306000_9.1.38.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30038-8"},{"key":"2025082410222306000_9.1.38.10","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.021254"},{"key":"2025082410222306000_9.1.38.11","doi-asserted-by":"publisher","DOI":"10.1053\/jscd.2003.9"},{"key":"2025082410222306000_9.1.38.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2005.01.003"},{"key":"2025082410222306000_9.1.38.13","article-title":"Effect of treatment delay, stroke type, and thrombolysis on the effect of glyceryl trinitrate, a nitric oxide donor, on outcome after acute stroke: a systematic review and meta-analysis of individual patient from randomised trials","volume":"2016","author":"Bath","year":"2016","journal-title":"Stroke Res Treat"},{"key":"2025082410222306000_9.1.38.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30194-1"},{"key":"2025082410222306000_9.1.38.15","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1161\/STROKEAHA.119.026389","article-title":"Prehospital transdermal glyceryl trinitrate for ultra-acute intracerebral hemorrhage: data from the RIGHT-2 trial","volume":"50","author":"Bath","year":"2019","journal-title":"Stroke"},{"key":"2025082410222306000_9.1.38.16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1177\/1747493017724627","article-title":"Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 (RIGHT-2) trial (ISRCTN26986053)","volume":"14","author":"Appleton","year":"2019","journal-title":"Int J Stroke"},{"key":"2025082410222306000_9.1.38.17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1177\/2396987318756696","article-title":"Statistical analysis plan for the \u201c rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 (RIGHT-2). \u201d","volume":"3","author":"Scutt","year":"2018","journal-title":"Eur Stroke J"},{"key":"2025082410222306000_9.1.38.18","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1177\/1747493018816451","article-title":"Baseline characteristics of the 1149 patients recruited into the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 (RIGHT-2) randomized controlled trial","volume":"14","author":"Bath","year":"2019","journal-title":"Int J Stroke"},{"key":"2025082410222306000_9.1.38.19","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.571562"},{"key":"2025082410222306000_9.1.38.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00012-5"},{"key":"2025082410222306000_9.1.38.21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008881"},{"key":"2025082410222306000_9.1.38.22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108784","article-title":"Applications of the wei-lachin multivariate one-sided test for multiple outcomes on possibly different scales","volume":"9","author":"Lachin","year":"2014","journal-title":"PLoS One"},{"key":"2025082410222306000_9.1.38.23","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1042\/CS20160382","article-title":"Hypercholesterolaemia and vascular dementia","volume":"131","author":"Appleton","year":"2017","journal-title":"Clin Sci (Lond)"},{"key":"2025082410222306000_9.1.38.24","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009647"},{"key":"2025082410222306000_9.1.38.25","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.001301"}],"container-title":["Stroke and Vascular Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/svn-2022-001634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T17:22:34Z","timestamp":1756056154000},"score":1,"resource":{"primary":{"URL":"https:\/\/svn.bmj.com\/lookup\/doi\/10.1136\/svn-2022-001634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,2,27]]},"published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1136\/svn-2022-001634"],"URL":"https:\/\/doi.org\/10.1136\/svn-2022-001634","relation":{},"ISSN":["2059-8688","2059-8696"],"issn-type":[{"value":"2059-8688","type":"print"},{"value":"2059-8696","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,8]]}}}