학술논문
Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial
Document Type
Academic Journal
Author
Bath, Philip M; Scutt, Polly; Anderson, Craig S; Appleton, Jason P; Berge, Evind; Cala, Lesley; Dixon, Mark; England, Timothy M; Godolphin, Peter J; Havard, Diane; Haywood, Lee; Hepburn, Trish; Krishnan, Kailash; Mair, Grant; Montgomery, Alan A; Muir, Keith; Phillips, Stephen J; Pocock, Stuart; Potter, John; Price, Chris; Randall, Marc; Robinson, Thompson G; Roffe, Christine; Rothwell, Peter M; Sandset, Else C; Sanossian, Nerses; Saver, Jeffrey L; Shone, Angela; Siriwardena, A Niroshan; Wardlaw, Joanna M; Woodhouse, Lisa J; Venables, Graham; Sprigg, Nikola; Amarenco, Pierre; Amoils, Shannon; Jarvis, Malcolm; Sandercock, Peter; Asplund, Kjell; Baigent, Colin; Ankolekar, Sandeep; Howard, Harriet; Lysons, Christopher; Walker, Gemma; Gregory, Hayley; Kirby, James; Smithson, Jennifer; Keeling, Joanne; Frowd, Nadia; Gray, Robert; Dooley, Richard; Clarke, Wim; Robinson, Patricia; Law, Zhe Kang; Hodgson, Sheila; Millington, Adam; Sakka, Eleni; Buchanan, David; Palmer, Jeb; Shaw, D; Cobb, H; Johnson, R; Payne, T; Spaight, R; Spaight, A; Sajid, M A; Whileman, A; Hall, E; Cripps, H; Toms, J; Gascoyne, R; Wright, S; Cooper, M; Palfreman, A; Rajapakse, A; Wynter, I; Musarrat, K; Mistri, A; Patel, C; Stephens, C; Khan, S; Patras, S; Soliman, M; Elmarimi, A; Hewitt, C; Watson, E; Wahishi, I; Hindle, J; Perkin, L; Wills, M; Arif, S; Leach, S; Butler, S; O'Kane, D; Smith, C; O'Callaghan, J; Sunman, W; Buck, A; Jackson, B; Richardson, C; Wilkes, G; Clarke, J; Ryan, L; Matias, O; Mangion, D; Hardwick, A; Constantin, C; Thomas, I; Netherton, K; Markova, S; Hedstrom, A; Rushton, B; Hyde, C; Scott, J; Blair, M; Maddula, M; Donnelly, R; Keane, S; Johnson, S; McKenzie, H; Banerjee, A; Hutchinson, D; Goodhand, H; Hill, J; Mellows, K; Cheeseman, M; McTaggart, V; Foster, T; Prothero, L; Saksena, P; O'Kelly, A; Wyllie, H; Hacon, C; Nutt, H; North, J; Goffin, K; Potter, J; Wiltshire, A; Ravenhill, G; Metcalf, K; Ford, L; Langley, M; Davison, W; Subramonian, S; Magezi, F; Obi, I; Temple, N; Butterworth-Cowin, N; Oqwusu-Agyei, P; Azim, A F M; Nicolson, A; Imam, J; White, J; Wood, L; Fothergill, R; Thompson, N; Lazarus, J; Werts, H; Sztriha, L; Ho, C; McKenzie, E; Owoyele, E; Lim, J; Aeron-Thomas, J; Dockey, M; Sylvester, N; Rao, P; Bloom, B M; Erumere, E; Norman, G; Skene, I; Cuenoud, L; Howaniec, L; Boulton, O; Daboo, P; Michael, R; Al-Saadi, S; Harrison, T; Syed, H; Argandona, L; Amiani, S; Perry, R; Ashton, A; Banaras, A; Hogan, C; Watchurst, C; Elliott, E; Francia, N; Oji, N; Erande, R; Obarey, S; Feerick, S; Tshuma, S; England, E; Pocock, H; Poole, K; Manchanda, S; Burn, I; Dayal, S; McNee, K; Robinson, M; Hancock, R; South, A; Holmes, C; Steele, A; Guthrie, L B; Oborn, M; Nor, A Mohd; Hyams, B; Eglinton, C; Waugh, D; Cann, E; Wilmhurst, N; Piesley, S; Shave, S; Dutta, D; Obeid, M; Ward, D; Turfrey, J; Glass, J; Bowstead, K; Hill, L; Brown, P; Beames, S; O'Connell, S; Hughes, V; Whiting, R; Gagg, J; Hussain, M; Harvey, M; Karunatilake, D; Pusuluri, B; Witcher, A; Pawley, C; Allen, J; Foot, J; Rowe, J; Lane, C; Ragab, S; Wadams, B; Dube, J; Jupp, B; Ljubez, A; Bagnall, C; Hann, G; Tucker, L; Kelton, M; Orr, S; Harrington, F; James, A; Lydon, A; Courtauld, G; Bond, K; Lucas, L; Nisbett, T; Kubie, J; Bowring, A; Jennings, G; Thorpe, K; Mason, N; Keenan, S; Gbadomishi, L; Howcroft, D; Newton, H; Choulerton, J; Avis, J; Shaw, L; Paterson, P; Kaye, P; Hierons, S; Lucas, S; Clatworthy, P; Faulkner, B; Rannigan, L; Worner, R; Bhaskaran, B; Saulat, A; Bearne, H; Garfield-Smith, J; Horan, K; Fitzell, P; Szabo, S; Haley, M; Simmons, D; Cotterill, D; Saunders, G; Dymond, H; Beech, S; Rashed, K; Tanate, A; Buckley, C; Wood, D; Matthews, L; Board, S; Pitt-Kirby, T; Rees, N; Convery, C; Jones, P; Bryant, C; Tench, H; Dixon, M; Loosley, R; Coetzee, S; Jones, S; Sims, T; Krishnan, M; Davies, C; Quinn, L; Connor, L; Wani, M; Storton, S; Treadwell, S; Anjum, T; Somashekar, C; Chandler, A; Triscott, C; Bevan, L; Sander, M; Buckle, S; Sayed, W; Andrews, K; Hughes, L; Hughes, R; Ward, M; Pretty, A; Rosser, A; Davidson, B; Price, G; Gunson, I; Lumley-Holmes, J; Miller, J; Larden, M; Jhamat, M; Horwood, P; Boldy, R; Jenkins, C; Price, F; Harrison, M; Martin, T; Ahmad, N; Willberry, A; Stevens, A; Fotherby, K; Barry, A; Remegoso, A; Alipio, F; Maquire, H; Hiden, J; Finney, K; Varquez, R; Ispoglou, S; Hayes, A; Gull, D; Evans, R; Epstein, E; Hurdowar, S; Crossley, J; Miles, J; Hird, K; Pilbery, R; Patterson, C; Ramadan, H; Stewart, K; Quinn, O; Bellfield, R; Macquire, S; Gaba, W; Nair, A; Wilson, A; Hawksworth, C; Alam, I; Greig, J; Gomes, P; Rana, P; Ahmed, Z; Anderston, P; Neal, A; Walstow, D; Fong, R; Brotheridge, S; Bwalya, A; Gillespie, A; Midgley, C; Hare, C; Lyon, H; Stephenson, L; Broome, M; Worton, R; Jackson, S; Rayessa, R; Abdul-Hamid, A; Naylor, C; Clarkson, E; Hassan, A; Veraque, E; Finch, L; Makawa, L; Carpenter, M; Datta, P; Needle, A; Jackson, L; Brooke, H J; Ball, J; Lowry, T; Punnoose, S; Walker, R; Murray, V; Ali, A; Kamara, C; Doyle, C; Richards, E; Howe, J; Dakin, K; Harkness, K; Lindert, R; Wanklyn, P; Willcoxson, P; Clark-Brown, P; Mir, R
Source
The Lancet. March 9, 2019, Vol. 393 Issue 10175, 1009
Subject
Language
English
ISSN
0140-6736
Abstract
Summary Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide 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 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances 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 of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 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%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5*8 mm Hg compared with the sham group (p Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting. Funding British Heart Foundation. * Correspondence to: Prof Philip M Bath, Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham City Hospital Campus, Nottingham NG5 1PB, UK (footnote)[Dagger] Members listed in the Byline: Philip M Bath [philip.bath@nottingham.ac.uk] (*), Polly Scutt, Craig S Anderson, Jason P Appleton, Evind Berge, Lesley Cala, Mark Dixon, Timothy M England, Peter J Godolphin, Diane Havard, Lee Haywood, Trish Hepburn, Kailash Krishnan, Grant Mair, Alan A Montgomery, Keith Muir, Stephen J Phillips, Stuart Pocock, John Potter, Chris 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, Pierre Amarenco, Keith Muir, Shannon Amoils, Malcolm Jarvis, Peter M Rothwell, Peter Sandercock, Kjell Asplund, Colin Baigent, Sandeep Ankolekar, Harriet Howard, Christopher Lysons, Gemma Walker, Hayley Gregory, James Kirby, Jennifer Smithson, Joanne Keeling, Nadia Frowd, Robert Gray, Richard Dooley, Wim Clarke, Patricia Robinson, Zhe Kang Law, Sheila Hodgson, Adam Millington, Eleni Sakka, David Buchanan, Jeb Palmer, D Shaw, H Cobb, R Johnson, T Payne, R Spaight, A Spaight, M A Sajid, A Whileman, E Hall, H Cripps, J Toms, R Gascoyne, S Wright, M Cooper, A Palfreman, A Rajapakse, I Wynter, K Musarrat, A Mistri, C Patel, C Stephens, S Khan, S Patras, M Soliman, A Elmarimi, C Hewitt, E Watson, I Wahishi, J Hindle, L Perkin, M Wills, S Arif, S Leach, S Butler, D O'Kane, C Smith, J O'Callaghan, W Sunman, A Buck, B Jackson, C Richardson, G Wilkes, J Clarke, L Ryan, O Matias, D Mangion, A Hardwick, C Constantin, I Thomas, K Netherton, S Markova, A Hedstrom, B Rushton, C Hyde, J Scott, M Blair, M Maddula, R Donnelly, S Keane, S Johnson, H McKenzie, A Banerjee, D Hutchinson, H Goodhand, J Hill, K Mellows, M Cheeseman, V McTaggart, T Foster, L Prothero, P Saksena, A O'Kelly, H Wyllie, C Hacon, H Nutt, J North, K Goffin, J Potter, A Wiltshire, G Ravenhill, K Metcalf, L Ford, M Langley, W Davison, S Subramonian, F Magezi, I Obi, N Temple, N Butterworth-Cowin, P Oqwusu-Agyei, A F M Azim, A Nicolson, J Imam, J White, L Wood, R Fothergill, N Thompson, J Lazarus, H Werts, L Sztriha, C Ho, E McKenzie, E Owoyele, J Lim, J Aeron-Thomas, M Dockey, N Sylvester, P Rao, B M Bloom, E Erumere, G Norman, I Skene, L Cuenoud, L Howaniec, O Boulton, P Daboo, R Michael, S Al-Saadi, T Harrison, H Syed, L Argandona, S Amiani, R Perry, A Ashton, A Banaras, C Hogan, C Watchurst, E Elliott, N Francia, N Oji, R Erande, S Obarey, S Feerick, S Tshuma, E England, H Pocock, K Poole, S Manchanda, I Burn, S Dayal, K McNee, M Robinson, R Hancock, A South, C Holmes, A Steele, L B Guthrie, M Oborn, A Mohd Nor, B Hyams, C Eglinton, D Waugh, E Cann, N Wilmhurst, S Piesley, S Shave, D Dutta, M Obeid, D Ward, J Turfrey, J Glass, K Bowstead, L Hill, P Brown, S Beames, S O'Connell, V Hughes, R Whiting, J Gagg, M Hussain, M Harvey, D Karunatilake, B Pusuluri, A Witcher, C Pawley, J Allen, J Foot, J Rowe, C Lane, S Ragab, B Wadams, J Dube, B Jupp, A Ljubez, C Bagnall, G Hann, L Tucker, M Kelton, S Orr, F Harrington, A James, A Lydon, G Courtauld, K Bond, L Lucas, T Nisbett, J Kubie, A Bowring, G Jennings, K Thorpe, N Mason, S Keenan, L Gbadomishi, D Howcroft, H Newton, J Choulerton, J Avis, L Shaw, P Paterson, P Kaye, S Hierons, S Lucas, P Clatworthy, B Faulkner, L Rannigan, R Worner, B Bhaskaran, A Saulat, H Bearne, J Garfield-Smith, K Horan, P Fitzell, S Szabo, M Haley, D Simmons, D Cotterill, G Saunders, H Dymond, S Beech, K Rashed, A Tanate, C Buckley, D Wood, L Matthews, S Board, T Pitt-Kirby, N Rees, C Convery, P Jones, C Bryant, H Tench, M Dixon, R Loosley, S Coetzee, S Jones, T Sims, M Krishnan, C Davies, L Quinn, L Connor, M Wani, S Storton, S Treadwell, T Anjum, C Somashekar, A Chandler, C Triscott, L Bevan, M Sander, S Buckle, W Sayed, K Andrews, L Hughes, R Hughes, M Ward, A Pretty, A Rosser, B Davidson, G Price, I Gunson, J Lumley-Holmes, J Miller, M Larden, M Jhamat, P Horwood, R Boldy, C Jenkins, F Price, M Harrison, T Martin, N Ahmad, A Willberry, A Stevens, K Fotherby, A Barry, A Remegoso, F Alipio, H Maquire, J Hiden, K Finney, R Varquez, S Ispoglou, A Hayes, D Gull, R Evans, E Epstein, S Hurdowar, J Crossley, J Miles, K Hird, R Pilbery, C Patterson, H Ramadan, K Stewart, O Quinn, R Bellfield, S Macquire, W Gaba, A Nair, A Wilson, C Hawksworth, I Alam, J Greig, M Robinson, P Gomes, P Rana, Z Ahmed, P Anderston, A Neal, D Walstow, R Fong, S Brotheridge, A Bwalya, A Gillespie, C Midgley, C Hare, H Lyon, L Stephenson, M Broome, R Worton, S Jackson, R Rayessa, A Abdul-Hamid, C Naylor, E Clarkson, A Hassan, D Waugh, E Veraque, L Finch, L Makawa, M Carpenter, P Datta, A Needle, L Jackson, H J Brooke, J Ball, T Lowry, S Punnoose, R Walker, V Murray, A Ali, C Kamara, C Doyle, E Richards, J Howe, K Dakin, K Harkness, R Lindert, P Wanklyn, P Willcoxson, P Clark-Brown, R Mir