@article{8bbe58a310b5412eb424fdbb62c35c6b,
title = "Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke",
abstract = "Objective: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS). Methods: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. Results: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2–24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). Interpretation: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211–218.",
author = "{for the Wake-Up Stroke Investigators} and Barreto, {Andrew D.} and Fanale, {Christopher V.} and Alexandrov, {Andrei V.} and Gaffney, {Kevin C.} and Vahidy, {Farhaan S.} and Nguyen, {Claude B.} and Amrou Sarraj and Mohammad Rahbar and Grotta, {James C.} and Savitz, {Sean I.} and Sands, {Kara A.} and Sheryl Martin-Schild and Navalkele, {Digvijaya D.} and Lopez, {George A.} and Wu, {Tzu Ching} and Gonzales, {Nicole R.} and Vivek Misra",
note = "Funding Information: This study was investigator initiated under an FDA-IND and supported by the Center for Clinical and Translational Sciences, which is funded by NIH Clinical and Translational Award UL1 RR024148 (TL1 RR024147 for the T32 program; KL2 RR0224149 for the K12 program) from the National Center for Research Resources (NCRR) and its renewal (UL1 TR000371) by the National Center for Advancing Translational Sciences (NCATS). The study was also supported by training grant 5-T32-NS007412-09 from the NIH to the University of Texas–Houston Medical School Stroke Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the NIH. We thank the members of the study Data Safety and Monitoring Board: Pitchaiah Mandava, MD, Raymond Martin, MD, and Ryan McDonald, MD. We are grateful for the clinical sites and investigators (in order of recruitment): Memorial Hermann–Texas Medical Center, Houston, Texas (28 cases); Colorado Neurological Institute (4 cases); Memorial Hermann–Southwest Hospital, Houston, Texas (6 cases); Memorial Hermann–The Woodlands Hospital, The Woodlands, Texas (1 case); and University of Alabama–Birmingham (1 case). We are grateful for the members of the Wake-Up Stroke Investigators: Kara A Sands, MD, Department of Neurology, Comprehensive Stroke Center, Department of Neurology; University of Alabama–Birmingham. Sheryl Martin-Schild, MD, PhD, and Digvijaya D. Navalkele, MD, MPH, Department of Neurology, Stroke Division; Tulane University Medical Center, New Orleans, Louisiana. George A. Lopez, MD, PhD, Rush University Medical Center, Chicago, Illinois. Tzu-Ching Wu, MD, and Nicole R. Gonzales, MD, Department of Neurology, Stroke Program; University of Texas Health Science Center at Houston, Houston, Texas. Vivek Misra, MD, Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Publisher Copyright: {\textcopyright} 2016 American Neurological Association",
year = "2016",
month = aug,
day = "1",
doi = "10.1002/ana.24700",
language = "English (US)",
volume = "80",
pages = "211--218",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley & Sons Inc.",
number = "2",
}