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

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; Niroshan Siriwardena, A; Wardlaw, Joanna M; Woodhouse, Lisa J; Venables, Graham; Sprigg, Nikola; Amarenco, Pierre; Muir, Keith; Amoils, Shannon; Jarvis, Malcolm; Rothwell, Peter M; 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; Kang Law, Zhe; 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; Mohd Nor, A; 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; Robinson, M; 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; Waugh, D; 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

doi:10.1016/S0140-6736(19)30194-1

The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke: A Review (2019)
Journal Article
Bath, P. M., Appleton, J. P., & England, T. (2020). The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke: A Review. JAMA Neurology, 77(1), 114-124. https://doi.org/10.1001/jamaneurol.2019.4107

Importance: While there are a limited number of beneficial treatments for acute stroke (eg, stroke units, reperfusion, aspirin, hemicraniectomy), there are more negative (as opposed to neutral) interventions spanning multiple different mechanisms of... Read More about The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke: A Review.

Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke (2019)
Journal Article
England, T. J., Hedstrom, A., O'Sullivan, S. E., Woodhouse, L., Jackson, B., & Sprigg, N. (2019). Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke. Journal of the American Heart Association, 8(23), https://doi.org/10.1161/JAHA.119.013572

Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage (2019)
Journal Article
Law, Z. K., Ali, A., Krishnan, K., Bischoff, A., Appleton, J., Scutt, P., …Sprigg, N. (2020). Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage. Stroke, 51(1), 121–128. https://doi.org/10.1161/STROKEAHA.119.026128

Background and purpose Blend, black hole and island signs and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage (ICH). We explored the value of these noncontrast CT (NCCT) signs in predicting hematoma expan... Read More about Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage.

Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage (2019)
Journal Article
Bath, P. M., Woodhouse, L. J., Krishnan, K., Appleton, J. P., Anderson, C. S., Berge, E., …Sprigg, N. (2019). Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage. Stroke, 50(11), 3064-3071. https://doi.org/10.1161/STROKEAHA.119.026389

Background and Purpose— Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, paramedic-delivered, ambulance-based, prospective ran... Read More about Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage.

Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT (2019)
Journal Article
Coates, E., Thomas, S. A., Drummond, A. E., Lincoln, N. B., Palmer, R. L., Sutherland, K. E., …Topcu, G. (2019). Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT. Health Technology Assessment, 23(47), 1-176. https://doi.org/10.3310/hta23470

Background: There is currently insufficient evidence for the clinical effectiveness and cost-effectiveness of psychological therapies for post-stroke depression. Objective: To evaluate the feasibility of undertaking a definitive trial to evaluate the... Read More about Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT.

Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT (2019)
Journal Article
Thomas, S. A., Drummond, A. E., Lincoln, N., Palmer, R., das Nair, R., Latimer, N. R., …Topcu, G. (2019). Behavioural activation therapy for post-stroke depression: the BEADS feasibility RCT. Health Technology Assessment, 23(47), https://doi.org/10.3310/hta23470

A systematic review of cannabidiol dosing in clinical populations (2019)
Journal Article
Millar, S. A., Stone, N., Bellman, Z., Yates, A., England, T., & O'Sullivan, S. (2019). A systematic review of cannabidiol dosing in clinical populations. British Journal of Clinical Pharmacology, 85(9), 1888-1900. https://doi.org/10.1111/bcp.14038

Aims: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied... Read More about A systematic review of cannabidiol dosing in clinical populations.

Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT (2019)
Journal Article
Sprigg, N., Flaherty, K., Appleton, J. P., Al-Shahi Salman, R., Bereczki, D., Beridze, M., …Bath, P. M. (2019). Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT. Health Technology Assessment, 23(35), 1-48. https://doi.org/10.3310/hta23350

BACKGROUND: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous... Read More about Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT.

A novel transwell blood brain barrier model using primary human cells (2019)
Journal Article
Stone, N. L., England, T. J., & O’Sullivan, S. E. (2019). A novel transwell blood brain barrier model using primary human cells. Frontiers in Cellular Neuroscience, 13, Article 230. https://doi.org/10.3389/fncel.2019.00230

© 2019 Stone, England and O’Sullivan. Structural alterations and breakdown of the blood brain barrier (BBB) is often a primary or secondary consequence of disease, resulting in brain oedema and the transport of unwanted substances into the brain. It... Read More about A novel transwell blood brain barrier model using primary human cells.

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial (2019)
Journal Article
Bath, P. M., Scutt, P., Anderson, C. S., Appleton, J. P., Berge, E., Cala, L., …Mir, R. (2019). Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial. Lancet, 393(10175), 1009-1020. https://doi.org/10.1016/S0140-6736%2819%2930194-1

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure... Read More about Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial.

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