Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)

Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, an...

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Main Authors: Appleton, Jason P., Scutt, Polly, Dixon, Mark, Howard, Harriet, Haywood, Lee, Havard, Diane, Hepburn, Trish, England, Timothy J., Sprigg, Nikola, Woodhouse, Lisa J., Wardlaw, Joanna M., Montgomery, Alan A., Pocock, Stuart J., Bath, Philip M.W.
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Published: SAGE 2017
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Online Access:https://eprints.nottingham.ac.uk/44928/
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author Appleton, Jason P.
Scutt, Polly
Dixon, Mark
Howard, Harriet
Haywood, Lee
Havard, Diane
Hepburn, Trish
England, Timothy J.
Sprigg, Nikola
Woodhouse, Lisa J.
Wardlaw, Joanna M.
Montgomery, Alan A.
Pocock, Stuart J.
Bath, Philip M.W.
author_facet Appleton, Jason P.
Scutt, Polly
Dixon, Mark
Howard, Harriet
Haywood, Lee
Havard, Diane
Hepburn, Trish
England, Timothy J.
Sprigg, Nikola
Woodhouse, Lisa J.
Wardlaw, Joanna M.
Montgomery, Alan A.
Pocock, Stuart J.
Bath, Philip M.W.
author_sort Appleton, Jason P.
building Nottingham Research Data Repository
collection Online Access
description Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim: To test the safety and efficacy of four days of transdermal glyceryl trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates: The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (glyceryl trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design: The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (4 h of onset) FAST-positive presumed stroke and systolic blood pressure 120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes: The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion: RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status: Trial is ongoing. Funding: British Heart Foundation. Registration: ISRCTN26986053.
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spelling nottingham-449282020-05-04T18:58:19Z https://eprints.nottingham.ac.uk/44928/ Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053) Appleton, Jason P. Scutt, Polly Dixon, Mark Howard, Harriet Haywood, Lee Havard, Diane Hepburn, Trish England, Timothy J. Sprigg, Nikola Woodhouse, Lisa J. Wardlaw, Joanna M. Montgomery, Alan A. Pocock, Stuart J. Bath, Philip M.W. Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as glyceryl trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim: To test the safety and efficacy of four days of transdermal glyceryl trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates: The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (glyceryl trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design: The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (4 h of onset) FAST-positive presumed stroke and systolic blood pressure 120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes: The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion: RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status: Trial is ongoing. Funding: British Heart Foundation. Registration: ISRCTN26986053. SAGE 2017-08-01 Article PeerReviewed Appleton, Jason P., Scutt, Polly, Dixon, Mark, Howard, Harriet, Haywood, Lee, Havard, Diane, Hepburn, Trish, England, Timothy J., Sprigg, Nikola, Woodhouse, Lisa J., Wardlaw, Joanna M., Montgomery, Alan A., Pocock, Stuart J. and Bath, Philip M.W. (2017) Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053). International Journal of Stroke . ISSN 1747-4949 Acute stroke ambulance antihypertensive therapy cerebrovascular disorders glyceryl trinitrate nitroglycerin paramedic randomized controlled trial http://journals.sagepub.com/doi/10.1177/1747493017724627 doi:10.1177/1747493017724627 doi:10.1177/1747493017724627
spellingShingle Acute stroke
ambulance
antihypertensive therapy
cerebrovascular disorders
glyceryl trinitrate
nitroglycerin
paramedic
randomized controlled trial
Appleton, Jason P.
Scutt, Polly
Dixon, Mark
Howard, Harriet
Haywood, Lee
Havard, Diane
Hepburn, Trish
England, Timothy J.
Sprigg, Nikola
Woodhouse, Lisa J.
Wardlaw, Joanna M.
Montgomery, Alan A.
Pocock, Stuart J.
Bath, Philip M.W.
Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title_full Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title_fullStr Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title_full_unstemmed Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title_short Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053)
title_sort ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: rationale, design and protocol for the rapid intervention with glyceryl trinitrate in hypertensive stroke trial-2 (right-2) trial (isrctn26986053)
topic Acute stroke
ambulance
antihypertensive therapy
cerebrovascular disorders
glyceryl trinitrate
nitroglycerin
paramedic
randomized controlled trial
url https://eprints.nottingham.ac.uk/44928/
https://eprints.nottingham.ac.uk/44928/
https://eprints.nottingham.ac.uk/44928/