M W Parsons1, F Miteff, G A Bateman, N Spratt, A Loiselle, J Attia, C R Levi. 1. Department of Neurology, Radiology, and Centre for Clinical Epidemiology and Biostatistics, John Hunter Hospital/Hunter Medical Research Institute, University of Newcastle, Australia. mark.parsons@hnehealth.nsw.gov.au
Abstract
BACKGROUND: Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase. METHODS: We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization. RESULTS: Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction > or = 8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours. CONCLUSIONS: Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.
BACKGROUND: Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase. METHODS: We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization. RESULTS: Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction > or = 8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours. CONCLUSIONS: Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.
Authors: Stephen Davis; Bruce Campbell; Soren Christensen; Henry Ma; Patricia Desmond; Mark Parsons; Christopher Levi; Christopher Bladin; P Alan Barber; Geoffrey Donnan Journal: Transl Stroke Res Date: 2012-04-18 Impact factor: 6.829
Authors: E Clarke Haley; John L P Thompson; James C Grotta; Patrick D Lyden; Thomas G Hemmen; Devin L Brown; Christopher Fanale; Richard Libman; Thomas G Kwiatkowski; Rafael H Llinas; Steven R Levine; Karen C Johnston; Richard Buchsbaum; Gilberto Levy; Bruce Levin Journal: Stroke Date: 2010-02-25 Impact factor: 7.914
Authors: Andrew Bivard; Venkatesh Krishnamurthy; Peter Stanwell; Nawaf Yassi; Neil J Spratt; Michael Nilsson; Christopher R Levi; Stephen Davis; Mark W Parsons Journal: J Cereb Blood Flow Metab Date: 2014-10-01 Impact factor: 6.200
Authors: Geoffrey A Donnan; Stephen M Davis; Mark W Parsons; Henry Ma; Helen M Dewey; David W Howells Journal: Nat Rev Neurol Date: 2011-06-14 Impact factor: 42.937