Pre-hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT-2 trial

Jason P Appleton; Mark Dixon; Lisa J Woodhouse; Craig S Anderson; Sandeep Ankolekar; Lesley Cala; Timothy J England; Peter J Godolphin; Kailash Krishnan; Grant Mair; Keith W Muir; John Potter; Chris I Price; Marc Randall; Thompson G Robinson; Christine Roffe; Peter M Rothwell; Else Charlotte Sandset; Jeffrey L Saver; A Niroshan Siriwardena; Joanna M Wardlaw; Nikola Sprigg; Philip M Bath; RIGHT‐2 Investigators

doi:10.1111/ene.16502

Pre-hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT-2 trial

Eur J Neurol. 2024 Dec;31(12):e16502. doi: 10.1111/ene.16502. Epub 2024 Oct 11.

Authors

Jason P Appleton^{1

2}, Mark Dixon^{2

3}, Lisa J Woodhouse², Craig S Anderson^{4

5

6}, Sandeep Ankolekar⁷, Lesley Cala⁸, Timothy J England², Peter J Godolphin⁹, Kailash Krishnan^{1

2}, Grant Mair¹⁰, Keith W Muir¹¹, John Potter¹², Chris I Price¹³, Marc Randall¹⁴, Thompson G Robinson¹⁵, Christine Roffe¹⁶, Peter M Rothwell¹⁷, Else Charlotte Sandset^{18

19}, Jeffrey L Saver²⁰, A Niroshan Siriwardena²¹, Joanna M Wardlaw¹⁰, Nikola Sprigg^{1

2}, Philip M Bath^{1

2}; RIGHT‐2 Investigators

Affiliations

¹ Stroke, Nottingham University Hospitals NHS Trust, Nottingham, UK.
² Stroke Trials Unit, School of Medicine, University of Nottingham, Nottingham, UK.
³ East Midlands Ambulance Service NHS Trust, Nottingham, UK.
⁴ George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
⁵ George Institute, Peking University Health Science Center, Beijing, China.
⁶ Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, New South Wales, Australia.
⁷ Department of Neurology, King's College Hospital London, London, UK.
⁸ Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
⁹ MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
¹⁰ Centre for Clinical Brain Sciences, Edinburgh Imaging and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.
¹¹ Institute of Neurology and Psychology, University of Glasgow, Glasgow, UK.
¹² Bob Champion Research and Education Building, University of East Anglia, Norwich, UK.
¹³ Population Health Sciences Institute, Newcastle University, Newcastle, UK.
¹⁴ Neurology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹⁵ Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
¹⁶ Stroke Research in Stoke, School of Medicine, Keele University, Stoke-on-Trent, UK.
¹⁷ Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
¹⁸ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹⁹ Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway.
²⁰ Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
²¹ Community and Health Research Unit, University of Lincoln, Lincoln, UK.

Abstract

Background and purpose: Ambulance trials assessing interventions in suspected stroke patients will recruit patients with currently active symptoms that will resolve into transient ischaemic attack (TIA). The safety and efficacy of glyceryl trinitrate (GTN) in the pre-specified subgroup of patients with TIA in the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial 2 (RIGHT-2) was assessed.

Methods: RIGHT-2 was a pre-hospital-initiated multicentre randomized sham-controlled blinded-endpoint trial that randomized patients with presumed ultra-acute stroke within 4 h of symptom onset to transdermal GTN or sham. Final diagnosis was determined by site investigators. The primary outcome was a shift in modified Rankin Scale (mRS) scores at 90 days analysed using ordinal logistic regression reported as adjusted common odds ratio with 95% confidence intervals (CIs). Secondary outcomes included death or dependence (mRS >2).

Results: In all, 109 of 1149 (9.5%) patients had a final diagnosis of TIA (GTN 57, sham 52) with mean age 73 (SD 13) years, 19 (17.4%) had pre-morbid mRS >2, and onset to randomization was 80 min (interquartile range 49, 105). GTN lowered blood pressure by 7.4/5.2 mmHg compared with sham by hospital arrival. At day 90, GTN had no effect on shift in mRS scores (common odds ratio for increased dependence 1.47, 95% CI 0.70-3.11) but was associated with increased death or dependence (mRS >2): GTN 29 (51.8%) versus sham 23 (46.9%), odds ratio 3.86 (95% CI 1.09-13.59).

Conclusions: Pre-hospital ultra-acute transdermal GTN did not improve overall functional outcome in patients with investigator-diagnosed TIA compared with sham treatment.

Keywords: blood pressure; clinical trial; stroke; transient ischaemic attack.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Administration, Cutaneous*
Aged
Aged, 80 and over
Emergency Medical Services / methods
Female
Humans
Ischemic Attack, Transient* / drug therapy
Male
Middle Aged
Nitroglycerin* / administration & dosage
Treatment Outcome
Vasodilator Agents* / administration & dosage

Substances

Nitroglycerin
Vasodilator Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding