Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke

• Published in: Annals of neurology Vol. 80; no. 2; pp. 211 - 218
• Main 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.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2016; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Cerebral Hemorrhage - chemically induced; Female; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - adverse effects; Fibrinolytic Agents - therapeutic use; Hemorrhage; Humans; Infusions, Intravenous; Male; Middle Aged; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Severity of Illness Index; Stroke; Stroke - drug therapy; Time Factors; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - adverse effects; Tissue Plasminogen Activator - therapeutic use; Treatment Outcome; Young Adult
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.24700

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