Prospective, open‐label safety study of intravenous recombinant tissue plasminogen activator in wake‐up stroke. Issue 2 (12th July 2016)

• Record Type: Journal Article
• Authors: Barreto, Andrew D.; Fanale, Christopher V.; Alexandrov, Andrei V.; Gaffney, Kevin C.; Vahidy, Farhaan S.; Nguyen, Claude B.; Sarraj, Amrou; Rahbar, Mohammad; Grotta, James C.; Savitz, Sean I.
• Other Names: Sands Kara A investigator.; Martin‐Schild Sheryl investigator.; Navalkele Digvijaya D. investigator.; Lopez George A. investigator.; Wu Tzu‐Ching investigator.; Gonzales Nicole R. investigator.; Misra Vivek investigator.
• Is Part Of: Annals of neurology. Volume 80:Issue 2(2016:Aug.)
• Page Start: 211
• Page End: 218
• Publication Date: 2016-07-12
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24700
• Languages: English
• ISSNs: 0364-5134

Abstract

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