Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit

Andrew Bivard, Henry Zhao, Skye Coote, Bruce Campbell, Leonid Churilov, Nawaf Yassi, Bernard Yan, Michael Valente, Angelos Sharobeam, Anna Balabanski, Angela Dos Santos, Felix Ng, Francesca Langenberg, Michael Stephenson, Karen Smith, Steve Bernard, Vincent Thijs, Geoffrey Cloud, Philip Choi, Henry Ma, Tissa Wijeratne, Chushuang Chen, Liudmyla Olenko, Stephen M Davis, Geoffrey A Donnan, Mark Parsons, Andrew Bivard, Henry Zhao, Skye Coote, Bruce Campbell, Leonid Churilov, Nawaf Yassi, Bernard Yan, Michael Valente, Angelos Sharobeam, Anna Balabanski, Angela Dos Santos, Felix Ng, Francesca Langenberg, Michael Stephenson, Karen Smith, Steve Bernard, Vincent Thijs, Geoffrey Cloud, Philip Choi, Henry Ma, Tissa Wijeratne, Chushuang Chen, Liudmyla Olenko, Stephen M Davis, Geoffrey A Donnan, Mark Parsons

Abstract

Introduction: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase.

Objective: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion.

Methods and analysis: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival.

Ethics and dissemination: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences.

Trial registration number: NCT04071613.

Keywords: Computed tomography; Neurology; STROKE MEDICINE; Stroke.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study assessments and procedures. AEs, adverse events; CTA, CT angiography; HT, haemorrhagic transformation; MSU, mobile stroke unit.

References

    1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–8. 10.1056/NEJM199512143332401
    1. Thomalla G, Sobesky J, Köhrmann M, et al. . Two tales: hemorrhagic transformation but not parenchymal hemorrhage after thrombolysis is related to severity and duration of ischemia: MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours. Stroke; a journal of cerebral circulation 2007;38:313–8.
    1. Hacke W, Donnan G, Fieschi C, et al. . Association of outcome with early stroke treatment: pooled analysis of Atlantis, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768–74.
    1. Emberson J, Lees KR, Lyden P, et al. . Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. The Lancet 2014;384:1929–35. 10.1016/S0140-6736(14)60584-5
    1. Kawano H, Bivard A, Lin L, et al. . Perfusion computed tomography in patients with stroke thrombolysis. Brain : a journal of neurology 2017;140:684–91.
    1. Fassbender K, Grotta JC, Walter S, et al. . Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges. Lancet Neurol 2017;16:227–37. 10.1016/S1474-4422(17)30008-X
    1. Walter S, Kostopoulos P, Haass A, et al. . Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial. The Lancet Neurology 2012;11:397–404. 10.1016/S1474-4422(12)70057-1
    1. Ebinger M, Winter B, Wendt M, et al. . Effect of the use of ambulance-based thrombolysis on time to thrombolysis in acute ischemic stroke. JAMA 2014;311:1622–31. 10.1001/jama.2014.2850
    1. Zhao Z, Zhang J, Jiang X, et al. . Is endovascular treatment still good for ischemic stroke in real world?: a meta-analysis of randomized control trial and observational study in the last decade. Stroke; a journal of cerebral circulation 2020;51:3250–63.
    1. Kim J, Thayabaranathan T, Donnan GA, et al. . Global stroke statistics 2019. International Journal of Stroke 2020;15:819–38. 10.1177/1747493020909545
    1. Cooley SR, Zhao H, Campbell BCV. Mobile stroke units facilitate prehospital management of intracerebral hemorrhage. Stroke; a journal of cerebral circulation 2021:Strokeaha121034592.
    1. Ebinger M, Siegerink B, Kunz A, et al. . Association between dispatch of mobile stroke units and functional outcomes among patients with acute ischemic stroke in Berlin. JAMA 2021;325:454–66. 10.1001/jama.2020.26345
    1. Grotta JC, Yamal J-M, Parker SA, et al. . Prospective, multicenter, controlled trial of mobile stroke units. New England Journal of Medicine 2021;385:971–81. 10.1056/NEJMoa2103879
    1. Zhao H, Coote S, Easton D, et al. . Melbourne mobile stroke unit and reperfusion therapy: greater clinical impact of thrombectomy than thrombolysis. Stroke; a journal of cerebral circulation 2020;51:922–30.
    1. Fassbender K, Merzou F, Lesmeister M, et al. . Impact of mobile stroke units. J Neurol Neurosurg Psychiatry 2021;92:815–22. 10.1136/jnnp-2020-324005
    1. Melandri G, Vagnarelli F, Calabrese D. tnkase) in the treatment of acute myocardial infarction. Vasc Health Risk Manag 2009;5:249–56.
    1. Ibanez B, James S, Agewall S. Esc guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of cardiology (ESC). Eur Heart J 2017;2018:119–77.
    1. Johnston S, Brightwell R, Ziman M. Paramedics and pre-hospital management of acute myocardial infarction: diagnosis and reperfusion. Emergency Medicine Journal 2006;23:331–4. 10.1136/emj.2005.028118
    1. Parsons M, Spratt N, Bivard A, et al. . A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. New England Journal of Medicine 2012;366:1099–107. 10.1056/NEJMoa1109842
    1. Huang X, Cheripelli BK, Lloyd SM, et al. . Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. The Lancet Neurology 2015;14:368–76. 10.1016/S1474-4422(15)70017-7
    1. Bivard A, Huang X, McElduff P, et al. . Impact of computed tomography perfusion imaging on the response to tenecteplase in ischemic stroke: analysis of 2 randomized controlled trials. Circulation 2017;135:440–8. 10.1161/CIRCULATIONAHA.116.022582
    1. Campbell BCV, Mitchell PJ, Churilov L, et al. . Tenecteplase versus alteplase before thrombectomy for ischemic stroke. New England Journal of Medicine 2018;378:1573–82. 10.1056/NEJMoa1716405
    1. Logallo N, Novotny V, Assmus J, et al. . Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. The Lancet Neurology 2017;16:781–8. 10.1016/S1474-4422(17)30253-3
    1. Campbell BCV, Mitchell PJ, Churilov L, et al. . Effect of intravenous tenecteplase dose on cerebral reperfusion before thrombectomy in patients with large vessel occlusion ischemic stroke: the extend-ia tnk Part 2 randomized clinical trial. JAMA 2020;323:1257–65. 10.1001/jama.2020.1511
    1. Sarraj A, Hassan A, Savitz SI, et al. . Endovascular thrombectomy for mild strokes: how low should we go? Stroke 2018;49:2398–405. 10.1161/STROKEAHA.118.022114
    1. Lin L, Bivard A, Krishnamurthy V, et al. . Whole-Brain CT perfusion to quantify acute ischemic penumbra and core. Radiology 2016;279:876–87. 10.1148/radiol.2015150319
    1. Chen C, Bivard A, Lin L, et al. . Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke: a CT perfusion study. J Cereb Blood Flow Metab 2019;39:536–46. 10.1177/0271678X17744453
    1. Wahlgren N, Ahmed N, Dávalos A, et al. . Thrombolysis with alteplase for acute ischaemic stroke in the safe implementation of thrombolysis in Stroke-Monitoring study (SITS-MOST): an observational study. Lancet 2007;369:275–82. 10.1016/S0140-6736(07)60149-4
    1. Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med 2011;30:3267–84. 10.1002/sim.4102
    1. White IR, Horton NJ, Carpenter J, et al. . Strategy for intention to treat analysis in randomised trials with missing outcome data. BMJ 2011;342:d40. 10.1136/bmj.d40

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner