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.
RCT Entities:
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.
Authors: Polly Scutt; Jason P Appleton; Mark Dixon; Lisa J Woodhouse; Nikola Sprigg; Joanna M Wardlaw; Alan A Montgomery; Stuart Pocock; Philip M Bath Journal: Eur Stroke J Date: 2018-02-01
Authors: Charlotte K Billington; Jason P Appleton; Eivind Berge; Nikola Sprigg; Mark Glover; Philip M W Bath Journal: Br J Clin Pharmacol Date: 2018-10-10 Impact factor: 4.335
Authors: Jason P Appleton; Lisa J Woodhouse; Daniel Bereczki; Eivind Berge; Hanne K Christensen; Rónán Collins; John Gommans; George Ntaios; Serefnur Ozturk; Szabolcs Szatmari; Joanna M Wardlaw; Nikola Sprigg; Peter M Rothwell; Philip M Bath Journal: Stroke Date: 2019-02 Impact factor: 7.914
Authors: Bronwyn Tunnage; Lisa J Woodhouse; Mark Dixon; Craig Anderson; Sandeep Ankolekar; Jason Appleton; Lesley Cala; Timothy England; Kailash Krishnan; Diane Havard; Grant Mair; Keith Muir; Steve Phillips; John Potter; Christopher Price; Marc Randall; Thompson G Robinson; Christine Roffe; Else Sandset; Niro Siriwardena; Polly Scutt; Joanna M Wardlaw; Nikola Sprigg; Philip M Bath Journal: BMC Emerg Med Date: 2022-01-10
Authors: Paula Muñoz Venturelli; Jason P Appleton; Craig S Anderson; Philip M Bath Journal: Curr Neurol Neurosci Rep Date: 2018-09-18 Impact factor: 5.081
Authors: Jason P Appleton; Lisa J Woodhouse; Alessandro Adami; Jennifer L Becker; Eivind Berge; Lesley A Cala; Ana M Casado; Valeria Caso; Hanne K Christensen; Robert A Dineen; John Gommans; Panos Koumellis; Szabolcs Szatmari; Nikola Sprigg; Philip M Bath; Joanna M Wardlaw Journal: Neurology Date: 2019-12-27 Impact factor: 9.910
Authors: Philip M Bath; Lisa J Woodhouse; Kailash Krishnan; Jason P Appleton; Craig S Anderson; Eivind Berge; Lesley Cala; Mark Dixon; Timothy J England; Peter J Godolphin; Trish Hepburn; Grant Mair; Alan A Montgomery; Stephen J Phillips; John Potter; Chris I Price; Marc Randall; Thompson G Robinson; Christine Roffe; Peter M Rothwell; Else C Sandset; Nerses Sanossian; Jeffrey L Saver; A Niroshan Siriwardena; Graham Venables; Joanna M Wardlaw; Nikola Sprigg Journal: Stroke Date: 2019-10-07 Impact factor: 7.914