Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): results from the pilot randomised controlled trial

Shaw, Lisa; Price, Chris; McLure, Sally; Howel, Denise; McColl, Elaine; Younger, Paul; Ford, Gary A.

doi:10.1136/emermed-2013-202536

Cited by 50 publications

(60 citation statements)

References 17 publications

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“…Given that transdermal GTN is inexpensive (≈£5 per patient), safe, widely available and can be easily administered before hospitalization or brain imaging, these results, and those from the RIGHT pilot trial and a meta-analysis of preclinical stroke studies, 12,17 justify a further large study: the RIGHT-2 trial (http://right2-trial.org), which will further assess the safety and efficacy of GTN in 850 patients with ultra acute stroke who are recruited by paramedics in the prehospital ambulance environment using a protocol that builds on the earlier Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT), and Field Administration of Stroke TherapyMagnesium (FAST-Mag) trial. 17,42,43 SUPPLEMENTAL MATERIAL Supplemental Table I Numbers needed (NNT) to treat with 95% confidence intervals for outcomes at day 90 with analysis using ordinal and binary data. NNT is the number of people who need to be treated for one to change an outcome state.…”

Section: Strokementioning

confidence: 99%

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Woodhouse

Scutt

Krishnan

et al. 2015

Stroke

100

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T reatment options for acute ischemic stroke are limited to thrombolysis, aspirin, hemicraniectomy and stroke unit care, [1][2][3][4] and mechanical thrombectomy. [5][6][7] Although there are no definitive treatments for acute intracerebral hemorrhage, lowering blood pressure (BP) might be beneficial. 8 As a result, new interventions are still needed and, ideally, ones that are simple to administer and relevant irrespective of stroke type so that they can be given prehospital or immediately on admission to hospital before neuroimaging.Nitric oxide (NO) donors are a candidate treatment for acute stroke. [9][10][11] In preclinical studies, NO donors reduced lesion size and increased cerebral blood flow, but only if given early. 12 In multiple pilot randomized controlled trials, NO donors (specifically intravenous sodium nitroprusside and transdermal glyceryl trinitrate [GTN]) reduced BP, pulse pressure, variability, and peak systolic BP; maintained cerebral blood flow (in spite of BP reduction); and improved arterial compliance. [13][14][15][16][17] Although sodium nitroprusside attenuated platelet function, GTN had no effect on platelets, 13,14 suggesting that it could be given to patients whether they had ischemic or hemorrhagic stroke. In a small trial of GTN administered by paramedics before hospital admission (with median time toBackground and Purpose-Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset. Methods-Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset.Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes. Results-Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (P<0.01, P=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32-0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale admission of 55 minutes), GTN seemed to improve functional outcome, assessed as the modified Rankin Scale (mRS). 17When assessed in a large international trial involving patients with stroke within 48 hours, GTN was safe to administer but did not alter mRS, the primary outcome. 18The potential benefit of GTN when administered early 17 suggested that the...

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Section: Strokementioning

confidence: 99%

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Woodhouse

Scutt

Krishnan

et al. 2015

Stroke

100

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“…7 Recent pilot studies have assessed the feasibility of a prehospital BP-lowering strategy in patients with acute stroke symptoms using topical glyceryl trinitrate 8 and sublingual lisinopril. 9 At this point, however, the natural history of BP in the prehospital setting in patients with acute stroke symptoms is poorly understood. In contrast, the course of BP after hospital admission has been well described.…”

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confidence: 99%

Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics

et al. 2016

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Objective: To assess the natural history of prehospital blood pressure (BP) during emergency medical services (EMS) transport of suspected stroke and determine whether prehospital BP differs among types of patients with suspected stroke (ischemic stroke, TIA, intracerebral hemorrhage [ICH], or stroke mimic).Methods: A retrospective, cross-sectional, observational analysis of a centralized EMS database containing electronic records of patients transported by EMS to the emergency department (ED) with suspected stroke during an 18-month period was conducted. Hospital charts and neuroimaging were utilized to determine the final diagnosis (ischemic stroke, TIA, ICH, or stroke mimic). Conclusions: Prehospital SBP is higher in acute stroke relative to stroke mimics and highest in ICH. Given the stability of BP between initial EMS and ED measurements, it may be reasonable to test the feasibility and safety of prehospital antihypertensive therapy in patients with suspected acute stroke. Elevated hospital admission blood pressure (BP) in patients with acute stroke is common 1 and is associated with poor outcomes. [2][3][4][5] There is limited randomized clinical trial evidence that acute BP reduction improves outcomes after intracerebral hemorrhage (ICH). Results6 One of the hypothesized reasons for the modest treatment effect is that hematoma enlargement and clinical deterioration have already begun by the time antihypertensive therapy is administered. It has been suggested that initiation of BP reduction in the prehospital setting may improve the efficacy of this approach. Recent pilot studies have assessed the feasibility of a prehospital BP-lowering strategy in patients with acute stroke symptoms using topical glyceryl trinitrate 8 and sublingual lisinopril. 9 At this point, however, the natural history of BP in the prehospital setting in patients with acute stroke symptoms is poorly understood. In contrast, the course of BP after hospital admission has been well described. Pressures are highest at admission, begin to spontaneously decline almost immediately, 10 and this trend continues for several days.

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“…Patients in Combined Table 2 Trials that did not require written consent Treatment With Alteplase (Rt-PA) and Cerebrolysin ® in Acute Ischemic Hemispheric Stroke (CERE-LYSE) and Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST) had to provide subsequent written informed consent for inclusion in the trial. 26,37 In The Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients Study (PHANTOM-S), only deidentified data could be gathered from individuals unable to give informed consent; later telephone follow-up at 3 months required written informed consent, as mandated under German law. 9 In the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT), written informed consent was required by the patient or proxy at the hospital, after the first treatment dose had been given in the ambulance.…”

mentioning

confidence: 99%

“…On univariable analysis (of the entire dataset, including these 2 outlier trials), we found that trials of prehospital interventions were less likely to require written informed consent (p , 0.01). The prehospital interventions included 2 German trials of mobile stroke units with on-board imaging and thrombolysis capabilities (the only 2 cluster-randomized trials in this review), 8,9 a Swedish trial in which participants in the intervention arm were assigned a higher prehospital priority level by the emergency dispatch center, 28 and 3 trials with paramedic-initiated therapies: lisinopril (UK), 37 ischemic preconditioning (Finland), 39 and glycerol trinitrate (UK). 40 Of these prehospital trials, only one required written informed consent en route to the hospital.…”

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Effect of waivers of consent on recruitment in acute stroke trials

et al. 2016

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There is urgent need for clinical trials of novel interventions to reduce the burden of acute ischemic stroke. A key impediment to such trials is slow recruitment. Since obtaining written informed consent in the setting of acute stroke is especially challenging, some experts have endorsed relaxing the requirement for informed consent by permitting verbal consent or waivers to facilitate recruitment. This systematic review of 36 randomized controlled trials of acute interventions for ischemic stroke assesses whether alternatives to written informed consent are associated with increased recruitment rates. After the exclusion of 2 outlier trials that differed from other trials in conduct and interventions studied, no association was observed on univariable analysis (8.9 participants/month in trials requiring written consent vs 6.1 participants/month in trials with alternatives, p 5 0.43) or multivariable analysis (when adjusting for the number of centers, number of countries, and exclusions based on modified Rankin Scale scores). Alternatives to written informed consent in acute stroke trials may enable trial designs that would not be feasible otherwise. However, we did not find evidence that, within traditional trial designs, such alternatives are associated with faster recruitment. Despite sweeping advances in stroke prevention and treatment including cardiovascular risk modification, acute reperfusion therapies, extensive public education, the establishment of stroke centers and systems of care, and new technologies such as telemedicine and imagingbased patient selection for endovascular treatment, ischemic stroke remains a leading cause of major disability and death. In recognition of the continuing need to improve outcomes in acute ischemic stroke, the NIH recently established a network of more than 200 sites (NIH StrokeNet) to provide infrastructure for stroke clinical trials.1 However, one of the enduring challenges for most clinical trials (particularly for acute stroke trials) is slow recruitment, which poses a serious threat to feasibility and statistical power. The requirement for informed consent has been described as the rate-limiting step of acute stroke trials. 4 Obtaining informed consent for research poses numerous challenges for stroke clinical investigators. The stroke itself may render a patient aphasic or cognitively incapacitated. Multiple studies indicate that surrogate decision-makers, if available, are less willing to enroll incapacitated relatives in clinical research compared to when patients are given the option directly.5-7 The time window for intervention is narrow, which requires investigators to hastily obtain consent while preparing to deliver sometimes complex treatments. Recent trials testing hyperacute field-based interventions such as thrombolysis on mobile stroke units equipped with CT scanners have further narrowed the time window to obtain consent. 8,9 Finally, many established and investigational therapies involve a complex weighing of risks and benefits, such that m...

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Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): results from the pilot randomised controlled trial

Cited by 50 publications

References 17 publications

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

Prehospital systolic blood pressure is higher in acute stroke compared with stroke mimics

Effect of waivers of consent on recruitment in acute stroke trials

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