scholarly journals 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)

2017 ◽  
Vol 14 (2) ◽  
pp. 191-206 ◽  
Author(s):  
Jason P Appleton ◽  
Polly Scutt ◽  
Mark Dixon ◽  
Harriet Howard ◽  
Lee Haywood ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Sample Size ◽  
Modified Rankin Scale ◽  
Time Data ◽  
Serious Adverse Events ◽  
Discharge Disposition ◽  
Include Blood Pressure ◽  
Stroke Trial

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.

scholarly journals Baseline characteristics of the 1149 patients recruited into the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) randomized controlled trial

2018 ◽  
Vol 14 (3) ◽  
pp. 298-305 ◽  
Author(s):  
Philip M Bath ◽  
Polly Scutt ◽  
Jason P Appleton ◽  
Mark Dixon ◽  
Lisa J Woodhouse ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Controlled Trial ◽  
Nitric Oxide Donor ◽  
Main Trial ◽  
Randomized Controlled ◽  
Baseline Characteristics ◽  
The Uk ◽  
Stroke Trial

Background High blood pressure is common in acute stroke and associated with a worse functional outcome. Glyceryl trinitrate, a nitric oxide donor, lowers blood pressure in acute stroke and may improve outcome. Aims Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) tested the feasibility of performing a UK multicenter ambulance-based stroke trial, and the safety and efficacy of glyceryl trinitrate when administered by paramedics before hospital admission. Methods Paramedic-led ambulance-based multicenter prospective randomized single-blind blinded-endpoint parallel-group controlled trial of transdermal glyceryl trinitrate (given for four days) versus sham in patients with ultra-acute (<4 h) presumed stroke. Data are number (%), median (interquartile range) or mean (standard deviation). Results Recruitment ran from October 2015 to 31 May 2018. A total 1149 patients were recruited from eight UK ambulance services and taken to 54 acute hospitals. Baseline characteristics include: mean age 73 (15) years; female 555 (48%); median time from stroke to randomization 70 (45, 115) min; face-arm-speech scale score 2.6 (0.5); and blood pressure 162 (25)/92 (18) mmHg. The final diagnosis was ischemic stroke 52%, hemorrhagic stroke 13%, Transient Ischemic Attack (TIA) 9%, and mimic 25%. The main trial results will be presented in quarter 4 2018. The results will also be included in updated Cochrane systematic reviews, and individual patient data meta-analyses of all relevant randomized controlled trials. Conclusion It was feasible to perform a multicenter ambulance-based ultra-acute stroke trial in the UK and to treat with glyceryl trinitrate versus sham. The relatively unselected cohort of stroke patients is broadly representative of those admitted to hospital in the UK. Trial registration ISRCTN26986053.

scholarly journals Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage

Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3064-3071 ◽  
Author(s):  
Philip M. Bath ◽  
Lisa J. Woodhouse ◽  
Kailash Krishnan ◽  
Jason P. Appleton ◽  
Craig S. Anderson ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Glyceryl Trinitrate ◽  
Global Analysis ◽  
Mass Effect ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Prehospital Treatment ◽  
Acute Intracerebral Hemorrhage

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 randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results— Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions— Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN26986053.

scholarly journals It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis

2019 ◽  
Vol 4 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Jason P Appleton ◽  
Lisa J Woodhouse ◽  
Andrew Belcher ◽  
Daniel Bereczki ◽  
Eivind Berge ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischaemic Stroke ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Carotid Stenosis ◽  
Primary Outcome ◽  
Lower Blood ◽  
Bilateral Carotid ◽  
Using Data

BackgroundThere is concern that blood pressure (BP) lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis. We assessed the effect of glyceryl trinitrate (GTN) in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.MethodsENOS randomised 4011 patients with acute stroke and raised systolic BP (140–220 mm Hg) to transdermal GTN or no GTN within 48 hours of onset. Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split: <30%; 30–<50%; 50–<70%; ≥70%. Data are ORs with 95% CIs adjusted for baseline prognostic factors.Results2023 (60.5%) ischaemic stroke participants had carotid imaging. As compared with <30%, ≥70% ipsilateral stenosis was associated with an unfavourable shift in mRS (worse outcome) at 90 days (OR 1.88, 95% CI 1.44 to 2.44, p<0.001). Those with ≥70% stenosis who received GTN versus no GTN had a favourable shift in mRS (OR 0.56, 95% CI 0.34 to 0.93, p=0.024). In those with 50–<70% stenosis, continuing versus stopping prestroke antihypertensives was associated with worse disability, mood, quality of life and cognition at 90 days. Clinical outcomes did not differ across bilateral stenosis groups.ConclusionsFollowing ischaemic stroke, severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days. GTN appears safe in ipsilateral or bilateral carotid stenosis, and might improve outcome in severe ipsilateral carotid stenosis.

BLOOD PRESSURE TREATMENT WITH CANDESARTAN IN ACUTE STROKE:THE SCANDINAVIAN CANDESARTAN ACUTE STROKE TRIAL

2011 ◽  
Vol 29 ◽  
pp. e18
Author(s):  
E. C. Sandset ◽  
P. M. W. Bath ◽  
G. Boysen ◽  
D. Jatuzis ◽  
J. Kõrv ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Stroke ◽  
Pressure Treatment ◽  
Blood Pressure Treatment ◽  
Stroke Trial

scholarly journals Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke

Stroke ◽  
2013 ◽  
Vol 44 (11) ◽  
pp. 3120-3128 ◽  
Author(s):  
Sandeep Ankolekar ◽  
Michael Fuller ◽  
Ian Cross ◽  
Cheryl Renton ◽  
Patrick Cox ◽  
...  
Keyword(s):  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Stroke Trial

scholarly journals Effect of Glyceryl Trinitrate on Hemodynamics in Acute Stroke

Stroke ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Jason P. Appleton ◽  
Lisa J. Woodhouse ◽  
Daniel Bereczki ◽  
Eivind Berge ◽  
Hanne K. Christensen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Mental State ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Mini Mental State Examination ◽  
Rate Pressure Product ◽  
Modified Rankin Scale ◽  
State Examination

Background and Purpose— Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods— Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results— Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65; 95% CI, 1.37–1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, −2.03; 95% CI, −2.84 to −1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57; 95% CI, 1.12–2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Conclusions— Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study.

scholarly journals INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lili Song ◽  
Chen Chen ◽  
Xiaoying Chen ◽  
Yijia Guo ◽  
Feifeng Liu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Stroke ◽  
Physical Function ◽  
Controlled Trial ◽  
Blood Pressure Reduction ◽  
Hematoma Expansion ◽  
Pressure Reduction ◽  
Open Label ◽  
Related Quality ◽  
Stroke Trial

Abstract Background Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). Methods A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of < 140 mmHg within 30 min, or guideline-recommended BP management according to local protocols. After the collection of in-hospital clinical and management data and 7-day outcomes, trained blinded assessors conduct telephone or face-to-face assessments of physical function and health-related quality of life in participants at 90 days. The primary outcome is the physical function on the modified Rankin scale at 90 days, analyzed as an ordinal outcome with 7 categories. The sample size was estimated to provide 90% power (α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. Discussion INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. Trial registration ClinicalTrials.gov NCT03790800. Registered on 2 January 2019; Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper.

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