Browsing by Author "Bath, P.M."

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Baseline characteristics of the 4011 patients recruited into the Efficacy of Nitric Oxide in Stroke' (ENOS) trial.
(Sage Publications, 2014) Bath, P.M.; Adami, A.; Bereczki, D.; Berge, E.; Beridze, M.; Cala, L.; Casado, A.; Caso, V.; Chang, H.M.; Christensen, H.; Collins, R.; Czlonkowska, A.; Dineen, R.A.; El Etribi, A.; Ghani, A. R.; Gommans, J.; Koumellis, P.; Laska, A. C.; Lees, K. R.; Navarro, J.; Ntaios, G.; Ozturk, S.; Phillips, S.; Pocock, S.; Prasad, K.; Scutt, P.; de Silva, H.A.; Szatmari, S.; Díez-Tejedor E; Utton, S.; Wang, Y. J.; Wardlaw, J.M.; Whynes, D.; Wong, L.; Woodhouse, L; Sprigg, N.; ENOS Trial Investigators(36)
BACKGROUND: High blood pressure is common in acute stroke and associated with a worse functional outcome. Many patients who present with acute stroke are taking prescribed antihypertensive therapy before their stroke. AIMS: ENOS tested whether lowering blood pressure and continuing pre-stroke antihypertensive therapy are each safe and effective. METHODS: This study is an international multi-centre prospective randomized single-blind blinded-endpoint parallel-group partial-factorial controlled trial of transdermal glyceryl trinitrate(a nitric oxide donor, given for seven-days) vs. no glyceryl trinitrate, and of continuing vs. stopping (temporarily for seven-days) pre-stroke antihypertensive drugs if relevant, in patients with acute ischaemic stroke or intracerebral haemorrhage and high systolic blood pressure (140–220 mmHg). RESULTS: Recruitment ran from July 2001 to October 2013. Four thousand eleven patients [2097 (52•3%) in the continue/stop arm] were recruited from 173 sites across 23 countries in 5 continents (Asia 14%, Continental Europe 16%, UK 64%). Baseline characteristics include: mean age 70 (standard deviation 12) years; male 57%; mean time from stroke to recruitment 26 (13) h; mean severity (Scandinavian Stroke Scale) 34(13) of 58; mean blood pressure 167 (19)/90 (13) mmHg; ischaemic stroke 83%; and intracerebral haemorrhage 16%. The main trial results will be presented in May 2014. The results will also be presented in updated Cochrane systematic reviews and included in individual patient data meta-analyses of all relevant randomized controlled trials. CONCLUSION: ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide.
Effect of the neutral CLOTS 1 trial on the use of graduated compression stockings in the Efficacy of Nitric Oxide Stroke (ENOS) trial
(BMJ Publishing Group, 2013) Ankolekar, S.; Renton, C.; Bereczki, D.; Sprigg, N.; Payne, T.; Gommans, J.; Berge, E.; Wardlaw, J.; Dennis, M.S.; Bath, P.M.; ENOS Trial Investigators; de Silva, A with 25 ENOS Trial Investigators
BACKGROUND AND PURPOSE: Current evidence suggests that the time lag from the publication of randomised clinical trial results to changes in prescribing behaviour for drugs is gradually reducing. However, the effect of results of clinical trials of devices and non-pharmacological interventions on clinical practice is less clear. METHODS: Prospective data from the ongoing international 'Efficacy of Nitric Oxide Stroke' (ENOS) trial were analysed to assess the use ofgraduated compression stockings (GCS) for deep vein thrombus (DVT) prophylaxis in acute stroke patients before and after publication of the large 'Clots in Legs Or sTockings after Stroke' (CLOTS-1) trial. RESULTS: Data on GCS use were available for 1971 patients with acute stroke enrolled into ENOS from February 2003 to April 2011; of these, 498 (25.3%) wore GCS. Prior to publication of CLOTS-1, GCS use was common (>50%) in the UK, Australasia and Canada but infrequent in Asia and the rest of Europe. After publication of CLOTS-1, use of GCS in the UK declined from 398/656 (61%) to 20/567 (4%) (p<0.001) but not elsewhere (eg, in Australasia (57% before publication vs 70% after publication, p=0.24, but based on small numbers). Practice change was apparent within 3 months of the study publication and was sustained thereafter. There was no change in DVT rates before and after CLOTS-1 (0.8% vs 1.0%). CONCLUSIONS : GCS use declined dramatically following the reporting of the CLOTS-1 trial. The results support the notion that a neutral trialof a device can influence clinical practice rapidly, which is important with a widely used and moderately expensive (time and finance) intervention
Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial
(Lancet Publishing Group, 2015) Bath, P.M.; Woodhouse, L; Scutt, P.; Krishnan, K.; Wardlaw, J.M.; Bereczki, D.; Sprigg, N.; Berge, E.; Beridze, M.; Caso, V.; Chen, C.; Christensen, H.; Collins, R.; El Etribi, A.; Laska, A. C.; Lees, K. R.; Ozturk, S.; Phillips, S.; Pocock, S.; de Silva, H.A.; Szatmari, S.; Utton, S.; ENOS Trial Investigators(955)
BACKGROUND: High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs to lower their blood pressure. METHODS: In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140–220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122. FINDINGS: Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7•0 [95% CI −8•5 to −5•6] mm Hg/–3•5 [–4•4 to −2•6] mm Hg; both p<0•0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9•5 [95% CI −11•8 to −7•2] mm Hg/–5•0 [–6•4 to −3•7] mm Hg; both p<0•0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1•01 (95% CI 0•91–1•13; p=0•83), and with continue versus stop antihypertensive drugs OR was 1•05 (0•90–1•22; p=0•55). INTERPRETATION: In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke. FUNDING: UK Medical Research Council.
Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis
(Dallas : American Heart Association, 2016) Krishnan, K.; Scutt, P.; Woodhouse, L.; Adami, A.; Becker, J.L.; Berge, E.; Cala, L.A.; Casado, A.M.; Caso, V.; Chen, C.; Christensen, H.; Collins, R.; Czlonkowska, A.; Dineen, R.A.; Gommans, J.; Koumellis, P.; Lees, K.R.; Ntaios, G.; Ozturk, S.; Phillips, S.J.; Pocock, S.J.; de Silva, A.; Sprigg, N.; Szatmari, S.; Wardlaw, J.M.; Bath, P.M.
BACKGROUND AND PURPOSE: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. CONCLUSIONS: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies.
Route of feeding as a proxy for dysphagia after stroke and the effect of transdermal Glyceryl Trinitrate: Data from the efficacy of nitric oxide in stroke randomised controlled trial
(Springer, 2018) Woodhouse, L.J.; Scutt, P.; Hamdy, S.; Smithard, D.G.; Cohen, D.L.; Roffe, C.; Bereczki, D.; Berge, E.; Bladin, C.F.; Caso, V.; Christensen, H.K.; Collins, R.; Czlonkowska, A.; de Silva, A.; Etribi, A.; Laska, A.C.; Ntaios, G.; Ozturk, S.; Phillips, S.J.; Prasad, K.; Szatmari, S.; Sprigg, N.; Bath, P.M.
Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between routeof feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke(ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feedingroute (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke. Clinical Trial Registration Clinical Trial Registration-URL: http://www.controlled-trials.com . Unique identifier: ISRCTN99414122.