Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms

Victor C Urrutia, Roland Faigle, Steven R Zeiler, Elisabeth B Marsh, Mona Bahouth, Mario Cerdan Trevino, Jennifer Dearborn, Richard Leigh, Susan Rice, Karen Lane, Mustapha Saheed, Peter Hill, Rafael H Llinas, Victor C Urrutia, Roland Faigle, Steven R Zeiler, Elisabeth B Marsh, Mona Bahouth, Mario Cerdan Trevino, Jennifer Dearborn, Richard Leigh, Susan Rice, Karen Lane, Mustapha Saheed, Peter Hill, Rafael H Llinas

Abstract

Background: Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria.

Methods: The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0-4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days.

Results: The average age was 65 years (range 47-83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4-11). The average time from wake-up to IV tPA was 205 minutes (range 114-270). The average time from last known well to IV tPA was 580 minutes (range 353-876). The median mRS at 90 days was 1 (range 0-5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging.

Conclusions: Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed.

Clinical trial registration: ClinicalTrials.gov NCT01643902.

Conflict of interest statement

Victor C. Urrutia: I have read the journal's policy and have the following conflicts: Genentech, Inc. provided funding (grant #ML28242) for the clinical trial (SAIL ON), which is the focus of this manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There are no employment, consultancy, patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flowchart of the SAIL…
Fig 1. CONSORT flowchart of the SAIL ON study.
Fig 2. Neuroimaging is shown for the…
Fig 2. Neuroimaging is shown for the two patients with asymptomatic hemorrhage.
Images (a) and (b) are from the 24 hour NCHCT on subject #2, images (c) and (d) are from the follow up MRI on subject #12. The arrows point to areas of hemorrhage.

References

    1. Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001;56(8):1015–20. .
    1. Fink JN, Kumar S, Horkan C, Linfante I, Selim MH, Caplan LR, et al. The stroke patient who woke up: clinical and radiological features, including diffusion and perfusion MRI. Stroke. 2002;33(4):988–93. .
    1. Nadeau JO, Fang J, Kapral MK, Silver FL, Hill MD, Registry of the Canadian Stroke N. Outcome after stroke upon awakening. Can J Neurol Sci. 2005;32(2):232–6. .
    1. Mackey J, Kleindorfer D, Sucharew H, Moomaw CJ, Kissela BM, Alwell K, et al. Population-based study of wake-up strokes. Neurology. 2011;76(19):1662–7. doi: ; PubMed Central PMCID: PMCPMC3100086.
    1. Demaerschalk BM, Yip TR. Economic benefit of increasing utilization of intravenous tissue plasminogen activator for acute ischemic stroke in the United States. Stroke. 2005;36(11):2500–3. doi: .
    1. Roveri L, La Gioia S, Ghidinelli C, Anzalone N, De Filippis C, Comi G. Wake-up stroke within 3 hours of symptom awareness: imaging and clinical features compared to standard recombinant tissue plasminogen activator treated stroke. J Stroke Cerebrovasc Dis. 2013;22(6):703–8. doi: .
    1. Koton S, Tanne D., Bornstein N. M. Ischemic Stroke on Awakening: Patient's characteristics, outcomes and potential for reperfusion therapy. Neuroepidemiology. 2012;39:149–53. doi:
    1. Jauch EC, Saver JL, Adams HP Jr., Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870–947. doi: .
    1. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29. doi: .
    1. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581–7. doi: .
    1. Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. .
    1. Agresti A, Coull BA. Approximate is better than "exact" for interval estimation of binomial proportions. The American Statistician. 1998;52(2):119–26.
    1. Barreto AD, Fanale CV, Alexandrov AV, Gaffney KC, Vahidy FS, Nguyen CB, et al. Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke. Ann Neurol. 2016;80(2):211–8. doi: .
    1. Thomalla G, Boutitie F, Fiebach JB, Simonsen CZ, Nighoghossian N, Pedraza S, et al. Stroke With Unknown Time of Symptom Onset: Baseline Clinical and Magnetic Resonance Imaging Data of the First Thousand Patients in WAKE-UP. Stroke. 2017. doi: .
    1. Schwamm LH, Wu O, Song SS, Latour L, Ford A, Hsia A, et al, for the MR WITNESS Investigators. IV Alteplase in MR-selected Patients With Stroke of Unknown Onset is Safe and feasible: Results if the Multicenter MR WITNESS Trial (NCT01282242). Presented at: International Stroke Conference, Los Angeles, CA. 2016.
    1. Barreto AD, Martin-Schild S, Hallevi H, Morales MM, Abraham AT, Gonzales NR, et al. Thrombolytic therapy for patients who wake-up with stroke. Stroke. 2009;40(3):827–32. doi: ; PubMed Central PMCID: PMCPMC2676861.
    1. Manawadu D, Bodla S, Keep J, Jarosz J, Kalra L. An observational study of thrombolysis outcomes in wake-up ischemic stroke patients. Stroke. 2013;44(2):427–31. doi: .
    1. Del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr., American Heart Association Stroke Council. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40(8):2945–8. doi: ; PubMed Central PMCID: PMCPMC2782817.
    1. Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al., on behalf of the American heart Association Stroke Council. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Regarding Endovascular Treatment. Stroke. 2015;46 doi:
    1. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375(9727):1695–703. doi: .
    1. Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CBLM, Dippel DW, et al. Time to Treatment with Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. JAMA. 2016;316(12):1279–88. doi:
    1. Schwamm LH, Ali SF, Reeves MJ, Smith EE, Saver JL, Messe S, et al. Temporal Trends in Patient Characteristics and Treatment With Intravenous Thrombolysis Among Acute Ischemic Stroke Patients at Get With the Guidelines-Stroke Hospitals. Circ Cardiovasc Qual Outcomes. 2013;6:543–9. doi:
    1. Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581–641. doi: .
    1. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. for the DAWN Trial Investigators. Thrombectomy 6 to 24 hours after Stroke with a mismatch between deficit and infarct. New England Journal of Medicine. 2017. Epub November 11, 2017. doi:
    1. Ginde AA, Foianini A, Renner DM, Valley M, Camargo CA Jr. Availability and quality of computed tomography and magnetic resonance imaging equipment in U.S. emergency departments. Acad Emerg Med. 2008;15(8):780–3. doi: .
    1. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 hours with selection by perfusion imaging. New England Journal of Medicine. 2018;378(8):708–18. Epub January 24, 2018. doi:

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel