Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Philip M. Bath, Polly Scutt, Craig Anderson, Sandeep Ankolekar, Jason P. Appleton, Eivind Berge, Lesley Cala, Mark Dixon, Timothy England, Peter Godolphin, Diane Harvard, Lee Haywood, Trish Hepburn, Kailash Krishnan, Grant Mair, Alan A. Montgomery, Keith Muir, Stephen J. Phillips, Stuart Pocock, John PotterChris Price, Marc Randall, Thompson G. Robinson, Christine Roffe, Peter M. Rothwell, Else C. Sandset, Nerses Sanossian, Jeffrey L. Saver, Angela Shone, A. Niroshan Siriwardena, Joanna M. Wardlaw, Lisa J. Woodhouse, Graham Venables, Nikola Sprigg

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Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials oflowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute strokeremains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitricoxide donor, might improve outcome when administered very early after stroke onset.Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled,blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receivetransdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbasedambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment,whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure offunctional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis washierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in allparticipants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. Thistrial is registered with ISRCTN, number ISRCTN26986053.Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min(IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) hadtransient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTNgroup, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001),and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference inmRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1):3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for pooroutcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2:3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found nodifference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group[p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatmentgroups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patientswith presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra acute prehospital setting
Original languageEnglish
Pages (from-to)1009-1020
Number of pages11
Issue number10175
Publication statusPublished - 6 Feb 2019

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