{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:11:04Z","timestamp":1773234664483,"version":"3.50.1"},"reference-count":30,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cerebrovasc Dis Extra"],"abstract":"<jats:p>Introduction: High blood pressure (BP) is associated with a poor outcome after stroke. Trials of transdermal glyceryl trinitrate (GTN), a nitric oxide donor, have suggested that treatment between 3 and 5 h might improve functional outcome. Methods: We randomly assigned hospitalised patients with an acute ischaemic or haemorrhagic stroke to 2 days of transdermal GTN (5 mg\/day) or sham, started between 3 and 5 h after onset. The primary feasibility outcome was recruitment rate; proof-of-concept (PoC) was assessed at 90 days by central observers blinded to treatment assignment using the modified Rankin Scale (mRS). Data are number (%), median [interquartile range], or mean (standard deviation). Comparisons were assessed by multiple linear regression. Results: Thirty-nine of an intended 120 participants were recruited. A total of 3,314 people were excluded, commonly related to presentation &gt;5 h of onset or outside of researcher working hours, no eligible symptoms\/signs or an unclear onset time. Mean age was 72 (SD 13) years, females were 41%, BP was 161.8 (18.4)\/80.8 (14.9) mm Hg, and time from onset at baseline was 216 [186, 251] minutes. The fall in BP over 24 h did not differ between GTN versus sham. mRS at 3 months did not differ between the groups (difference in means, DIM \u22120.20, 95% confidence intervals \u22121.30, 0.90; p = 0.72). GTN was associated with improved cognition on the telephone interview of cognition scale (DIM 8.0, 95% CI 1.3, 14.8; p = 0.020). Although headache was more common, GTN was associated with fewer serious adverse events (p = 0.020). Conclusion: Recruitment limitations in this small single-centre trial prevented demonstration of feasibility for patients in the time window of 3\u20135 h post ictus. GTN demonstrated some evidence of PoC and was safe. A multicentre trial needs to further test this hypothesis.<\/jats:p>","DOI":"10.1159\/000550499","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:00:54Z","timestamp":1768582854000},"page":"74-86","source":"Crossref","is-referenced-by-count":0,"title":["Glyceryl Trinitrate versus Sham in the Treatment of Hyperacute Stroke: The Efficacy of Nitric Oxide in Stroke-2 (ENOS-2) Feasibility Randomised Controlled Trial"],"prefix":"10.1159","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-1999","authenticated-orcid":false,"given":"Lisa 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