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Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage

Bath, Philip M.; Woodhouse, Lisa J.; Krishnan, Kailah; Appleton, Jason P.; Anderson, Craig S.; Berge, Eivind; Cala, Lesley; Dixon, Mark; England, Timothy J.; Godolphin, Peter J.; Hepburn, Trish; Mair, Grant; Montgomery, Alan A.; Phillips, Stephen J.; Potter, John; Price, Chris I.; Randall, Marc; Robinson, Thompson G.; Roffe, Christine; Rothwell, Peter M.; Sandset, Else C.; Sanossian, Nerses; Saver, Jeffrey L.; Siriwardena, A. Niroshan; Venables, Graham; Wardlaw, Joanna M.; Sprigg, Nikola

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage Thumbnail


Stroke Association Professor of Stroke Medicine

Kailah Krishnan

Jason P. Appleton

Craig S. Anderson

Eivind Berge

Lesley Cala

Mark Dixon

Peter J. Godolphin

Senior Medical Statistician

Grant Mair

Director Nottingham Clinical Trials Unit

Stephen J. Phillips

John Potter

Chris I. Price

Marc Randall

Thompson G. Robinson

Christine Roffe

Peter M. Rothwell

Else C. Sandset

Nerses Sanossian

Jeffrey L. Saver

A. Niroshan Siriwardena

Graham Venables

Joanna M. Wardlaw

Professor of Stroke Medicine


Background and Purpose—
Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset.

We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat.

Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events.

Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed.

Clinical Trial Registration—
URL: Unique identifier: ISRCTN26986053.

Journal Article Type Article
Acceptance Date Aug 13, 2019
Online Publication Date Oct 7, 2019
Publication Date Nov 1, 2019
Deposit Date Sep 25, 2019
Publicly Available Date Nov 1, 2019
Journal Stroke
Print ISSN 0039-2499
Electronic ISSN 1524-4628
Publisher American Heart Association
Peer Reviewed Peer Reviewed
Volume 50
Issue 11
Pages 3064-3071
Keywords Advanced and Specialised Nursing; Clinical Neurology; Cardiology and Cardiovascular Medicine
Public URL
Publisher URL


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