Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): study protocol for a pilot randomised controlled trial

Lisa Shaw, Christopher Price, Sally McLure, Denise Howel, Elaine McColl, Gary A Ford, Lisa Shaw, Christopher Price, Sally McLure, Denise Howel, Elaine McColl, Gary A Ford

Abstract

Background: High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics). However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke.

Trial design: Double blind parallel group external pilot randomised controlled trial.

Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals.

Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset) and hypertension (systolic BP>160 mmHg).

Intervention: Lisinopril 5-10 mg (intervention group), matched placebo (control group), daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics.

Outcomes: Study feasibility (recruitment rate, compliance with data collection) and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function).

Discussion: This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke.

Trial registration: EudraCT: 2010-019180-10ClinicalTrials.gov: NCT01066572ISRCTN: 54540667.

Figures

Figure 1
Figure 1
Study method.

References

    1. Willmot M, Leonardi-Bee J, Bath PMW. High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension. 2004;43:18–24. doi: 10.1161/01.HYP.0000118134.56524.b1.
    1. Sare GM, Ali M, Shuaib A, Bath PMW. Vista Collaboration. Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA collaboration. Stroke. 2009;40:2098–2103. doi: 10.1161/STROKEAHA.108.539155.
    1. Reinhard M, Wihler C, Roth M, Harloff A, Niesen W-D, Timmer J, Weiller C, Hetzel A. Cerebral autoregulation dynamics in acute ischemic stroke after rtPA thrombolysis. Cerebrovascular Diseases. 2008;26:147–155. doi: 10.1159/000139662.
    1. Ahmed N, Wahlgren G. High initial blood pressure after acute stroke is associated with poor functional outcome. Journal of Internal Medicine. 2001;249:467–473. doi: 10.1046/j.1365-2796.2001.00831.x.
    1. Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG. Group ISTC. Blood pressure and clinical outcomes in the International Stroke Trial. Stroke. 2002;33:1315–1320. doi: 10.1161/01.STR.0000014509.11540.66.
    1. Geeganage C, Bath PMW. Interventions for deliberately altering blood pressure in acute stroke. Cochrane Database of Systematic Reviews. 2008. p. CD000039.
    1. Sandset EC, Bath PM, Boysen G, Jatuzis D, Korv J, Luders S, Murray GD, Richter PS, Roine RO, Terent A. et al.The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011;377:741–750. doi: 10.1016/S0140-6736(11)60104-9.
    1. Geeganage C, Bath PMW. Vasoactive drugs for acute stroke. Cochrane Database of Systematic Reviews. 2010. p. CD002839.
    1. Saver JL. Time is brain--quantified. Stroke. 2006;37:263–266.
    1. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr. et al.Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363:768–774.
    1. Delcourt C, Huang Y, Wang J, Heeley E, Lindley R, Stapf C, Tzourio C, Arima H, Parsons M, Sun J. et al.The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT2) International Journal of Stroke. 2010;5:110–116. doi: 10.1111/j.1747-4949.2010.00415.x.
    1. Antihypertensive Treatment in Acute Cerebral Hemorrhage - II (ATACH-II)
    1. Brazier H, Murphy AW, Lynch C, Bury G. Searching for the evidence in pre-hospital care: a review of randomised controlled trials. On behalf of the Ambulance Response Time Sub-Group of the National Ambulance Advisory Committee. Journal of Accident & Emergency Medicine. 1999;16:18–23.
    1. Snooks H, Evans A, Wells B, Peconi J, Thomas M. What are the highest priorities for research in pre-hospital care? Results of a review and Delphi consultation exercise. Journal of Emergency Primary Health Care. 2008;6
    1. Saver JL, Kidwell C, Eckstein M, Starkman S, Investigators F-MPT, Saver JL, Kidwell C, Eckstein M, Starkman S. Prehospital neuroprotective therapy for acute stroke: results of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) pilot trial. Stroke. 2004;35:e106–108. doi: 10.1161/01.STR.0000124458.98123.52.
    1. Medical Care Research Unit University of Sheffield. Building the evidence base in pre-hospital urgent and emergency care: A review of research evidence and priorities for future research. Department of Health; 2010.
    1. Siriwardena AN, Donohoe R, Stephenson J, Phillips P. Supporting research and development in ambulance services: research for better health care in prehospital settings. Emergency Medicine Journal. 2010;27:324–326. doi: 10.1136/emj.2009.072363.
    1. Morrison LJ, Long J, Vermeulen M, Schwartz B, Sawadsky B, Frank J, Cameron B, Burgess R, Shield J, Bagley P. et al.A randomized controlled feasibility trial comparing safety and effectiveness of prehospital pacing versus conventional treatment: 'PrePACE'. Resuscitation. 2008;76:341–349. doi: 10.1016/j.resuscitation.2007.08.008.
    1. Morrison LJ, Baker AJ, Rhind SG, Kiss A, MacDonald RD, Schwartz B, Perreira T, Simitciu M, Trompeo A, Black SE, The Toronto prehospital hypertonic resuscitation - head injury and multiorgan dysfunction trial: Feasibility study of a randomised controlled trial. Journal of Critical Care. 2010. in press .
    1. Lancaster GA, Dodd S, Williamson PR, Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. Journal of Evaluation in Clinical Practice. 2004;10:307–312. doi: 10.1111/j..2002.384.doc.x.
    1. Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L, Goldsmith CH. et al.A tutorial on pilot studies: the what, why and how. BMC Medical Research Methodology. 2010;10:1. doi: 10.1186/1471-2288-10-1.
    1. Potter JF, Robinson TG, Ford GA, Mistri A, James M, Chernova J, Jagger C. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurology. 2009;8:48–56. doi: 10.1016/S1474-4422(08)70263-1.
    1. Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V. et al.Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864–870. doi: 10.1161/01.STR.20.7.864.
    1. Mahoney FI, Barthel DW. Functional Evaluation: the Barthel Index. Maryland State Medical Journal. 1965;14:61–65.
    1. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–607. doi: 10.1161/01.STR.19.5.604.
    1. Department of Health Scientific Development and Bioethics Division. Guidance on nominating a consultee for research involving adults who lack capacity to consent. Department of Health; 2008.
    1. Crash Trial Management Group. Research in emergency situations: with or without relatives consent. Emergency Medicine Journal. 2004;21:703.
    1. Flaherty ML, Karlawish J, Khoury JC, Kleindorfer D, Woo D, Broderick JP. How important is surrogate consent for stroke research? Neurology. 2008;71:1566–1571. doi: 10.1212/01.wnl.0000316196.63704.f5.
    1. The Third International Stroke Trial.
    1. Stroke Oxygen Study.
    1. Medicines for Human Use (Clinical Trials) Regulations.
    1. ICH Harmonised Tripartite Guideline for Good Clinical Practice.
    1. Department of Health. Research Governance Framework for Health and Social Care. 2. Department of Health; 2005.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться