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


CONCLUSIONS
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.
Department of Neurology, Stroke Program; University of Texas Health Science Center at Houston, Houston, TX.
Andrew D
AD
Barreto
Colorado Research Institute, Englewood, CO.
Christopher V
CV
Fanale
Department of Neurology, Stroke Program; University of Tennessee, Memphis, TN.
Andrei V
AV
Alexandrov
Memorial Hermann Hospital-The Woodlands, The Woodlands, TX.
Kevin C
KC
Gaffney
Department of Neurology, Stroke Program; University of Texas Health Science Center at Houston, Houston, TX.
Farhaan S
FS
Vahidy
Department of Neurology, University of Pennsylvania Hospital, Philadelphia, PA.
Claude B
CB
Nguyen
Department of Neurology, Stroke Program; University of Texas Health Science Center at Houston, Houston, TX.
Amrou
A
Sarraj
A) Division of Clinical and Translational Sciences, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, B) Division of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX, and C) Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), University of Texas Health Science Center at Houston, Houston, TX.
Mohammad
M
Rahbar
Clinical Innovation and Research Institute, Memorial Hermann Hospital-Texas Medical Center, Houston, TX.
James C
JC
Grotta
Department of Neurology, Stroke Program; University of Texas Health Science Center at Houston, Houston, TX.
Sean I
SI
Savitz
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator