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 and Scutt, Polly and Anderson, Craig S and Appleton, Jason P and Berge, Evind and Cala, Lesley and Dixon, Mark and England, Timothy M and Godolphin, Peter J and Havard, Diane and Haywood, Lee and Hepburn, Trish and Krishnan, Kailash and Mair, Grant and Montgomery, Alan A and Muir, Keith and Phillips, Stephen J and Pocock, Stuart and Potter, John and Price, Chris and Randall, Marc and Robinson, Thompson G and Roffe, Christine and Rothwell, Peter M and Sandset, Else C and Sanossian, Nerses and Saver, Jeffrey L and Shone, Angela and Siriwardena, A Niroshan and Wardlaw, Joanna M and Woodhouse, Lisa J and Venables, Graham and Sprigg, Nikola and Amarenco, Pierre and Muir, Keith and Amoils, Shannon and Jarvis, Malcolm and Rothwell, Peter M and Sandercock, Peter and Asplund, Kjell and Baigent, Colin and Ankolekar, Sandeep and Howard, Harriet and Lysons, Christopher and Walker, Gemma and Gregory, Hayley and Kirby, James and Smithson, Jennifer and Keeling, Joanne and Frowd, Nadia and Gray, Robert and Dooley, Richard and Clarke, Wim and Robinson, Patricia and Law, Zhe Kang and Hodgson, Sheila and Millington, Adam and Sakka, Eleni and Buchanan, David and Palmer, Jeb and Shaw, D and Cobb, H and Johnson, R and Payne, T and Spaight, R and Spaight, A and Sajid, M A and Whileman, A and Hall, E and Cripps, H and Toms, J and Gascoyne, R and Wright, S and Cooper, M and Palfreman, A and Rajapakse, A and Wynter, I and Musarrat, K and Mistri, A and Patel, C and Stephens, C and Khan, S and Patras, S and Soliman, M and Elmarimi, A and Hewitt, C and Watson, E and Wahishi, I and Hindle, J and Perkin, L and Wills, M and Arif, S and Leach, S and Butler, S and O'Kane, D and Smith, C and O'Callaghan, J and Sunman, W and Buck, A and Jackson, B and Richardson, C and Wilkes, G and Clarke, J and Ryan, L and Matias, O and Mangion, D and Hardwick, A and Constantin, C and Thomas, I and Netherton, K and Markova, S and Hedstrom, A and Rushton, B and Hyde, C and Scott, J and Blair, M and Maddula, M and Donnelly, R and Keane, S and Johnson, S and McKenzie, H and Banerjee, A and Hutchinson, D and Goodhand, H and Hill, J and Mellows, K and Cheeseman, M and McTaggart, V and Foster, T and Prothero, L and Saksena, P and O'Kelly, A and Wyllie, H and Hacon, C and Nutt, H and North, J and Goffin, K and Potter, J and Wiltshire, A and Ravenhill, G and Metcalf, K and Ford, L and Langley, M and Davison, W and Subramonian, S and Magezi, F and Obi, I and Temple, N and Butterworth-Cowin, N and Oqwusu-Agyei, P and Azim, A F M and Nicolson, A and Imam, J and White, J and Wood, L and Fothergill, R and Thompson, N and Lazarus, J and Werts, H and Sztriha, L and Ho, C and McKenzie, E and Owoyele, E and Lim, J and Aeron-Thomas, J and Dockey, M and Sylvester, N and Rao, P and Bloom, B M and Erumere, E and Norman, G and Skene, I and Cuenoud, L and Howaniec, L and Boulton, O and Daboo, P and Michael, R and Al-Saadi, S and Harrison, T and Syed, H and Argandona, L and Amiani, S and Perry, R and Ashton, A and Banaras, A and Hogan, C and Watchurst, C and Elliott, E and Francia, N and Oji, N and Erande, R and Obarey, S and Feerick, S and Tshuma, S and England, E and Pocock, H and Poole, K and Manchanda, S and Burn, I and Dayal, S and McNee, K and Robinson, M and Hancock, R and South, A and Holmes, C and Steele, A and Guthrie, L B and Oborn, M and Nor, A Mohd and Hyams, B and Eglinton, C and Waugh, D and Cann, E and Wilmhurst, N and Piesley, S and Shave, S and Dutta, D and Obeid, M and Ward, D and Turfrey, J and Glass, J and Bowstead, K and Hill, L and Brown, P and Beames, S and O'Connell, S and Hughes, V and Whiting, R and Gagg, J and Hussain, M and Harvey, M and Karunatilake, D and Pusuluri, B and Witcher, A and Pawley, C and Allen, J and Foot, J and Rowe, J and Lane, C and Ragab, S and Wadams, B and Dube, J and Jupp, B and Ljubez, A and Bagnall, C and Hann, G and Tucker, L and Kelton, M and Orr, S and Harrington, F and James, A and Lydon, A and Courtauld, G and Bond, K and Lucas, L and Nisbett, T and Kubie, J and Bowring, A and Jennings, G and Thorpe, K and Mason, N and Keenan, S and Gbadomishi, L and Howcroft, D and Newton, H and Choulerton, J and Avis, J and Shaw, L and Paterson, P and Kaye, P and Hierons, S and Lucas, S and Clatworthy, P and Faulkner, B and Rannigan, L and Worner, R and Bhaskaran, B and Saulat, A and Bearne, H and Garfield-Smith, J and Horan, K and Fitzell, P and Szabo, S and Haley, M and Simmons, D and Cotterill, D and Saunders, G and Dymond, H and Beech, S and Rashed, K and Tanate, A and Buckley, C and Wood, D and Matthews, L and Board, S and Pitt-Kirby, T and Rees, N and Convery, C and Jones, P and Bryant, C and Tench, H and Dixon, M and Loosley, R and Coetzee, S and Jones, S and Sims, T and Krishnan, M and Davies, C and Quinn, L and Connor, L and Wani, M and Storton, S and Treadwell, S and Anjum, T and Somashekar, C and Chandler, A and Triscott, C and Bevan, L and Sander, M and Buckle, S and Sayed, W and Andrews, K and Hughes, L and Hughes, R and Ward, M and Pretty, A and Rosser, A and Davidson, B and Price, G and Gunson, I and Lumley-Holmes, J and Miller, J and Larden, M and Jhamat, M and Horwood, P and Boldy, R and Jenkins, C and Price, F and Harrison, M and Martin, T and Ahmad, N and Willberry, A and Stevens, A and Fotherby, K and Barry, A and Remegoso, A and Alipio, F and Maquire, H and Hiden, J and Finney, K and Varquez, R and Ispoglou, S and Hayes, A and Gull, D and Evans, R and Epstein, E and Hurdowar, S and Crossley, J and Miles, J and Hird, K and Pilbery, R and Patterson, C and Ramadan, H and Stewart, K and Quinn, O and Bellfield, R and Macquire, S and Gaba, W and Nair, A and Wilson, A and Hawksworth, C and Alam, I and Greig, J and Robinson, M and Gomes, P and Rana, P and Ahmed, Z and Anderston, P and Neal, A and Walstow, D and Fong, R and Brotheridge, S and Bwalya, A and Gillespie, A and Midgley, C and Hare, C and Lyon, H and Stephenson, L and Broome, M and Worton, R and Jackson, S and Rayessa, R and Abdul-Hamid, A and Naylor, C and Clarkson, E and Hassan, A and Waugh, D and Veraque, E and Finch, L and Makawa, L and Carpenter, M and Datta, P and Needle, A and Jackson, L and Brooke, H J and Ball, J and Lowry, T and Punnoose, S and Walker, R and Murray, V and Ali, A and Kamara, C and Doyle, C and Richards, E and Howe, J and Dakin, K and Harkness, K and Lindert, R and Wanklyn, P and Willcoxson, P and Clark-Brown, P and 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. The Lancet, 393 . pp. 1009-1020. ISSN 0140-6736

Full content URL: http://doi.org/10.1016/S0140-6736(19)30194-1

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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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Abstract

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<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS 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 poor outcome 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 no difference 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 treatment groups.
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 ultraacute prehospital setting.
Funding British Heart Foundation.

Keywords:stroke, glycereyl trinitrate, randomised controlled trial, paramedic, ambulance, prehospital, transient ischaemic attack, blood pressure
Subjects:B Subjects allied to Medicine > B780 Paramedical Nursing
B Subjects allied to Medicine > B740 Adult Nursing
A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Social Science > School of Health & Social Care
ID Code:34942
Deposited On:27 Mar 2019 09:00

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