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

for the Wake-Up Stroke Investigators

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalAnnals of Neurology
Volume80
Issue number2
DOIs
StatePublished - Aug 1 2016

Fingerprint

Tissue Plasminogen Activator
Stroke
Safety
Cerebral Hemorrhage
National Institutes of Health (U.S.)
Lost to Follow-Up
Middle Cerebral Artery
Hematoma
Tomography

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke. / for the Wake-Up Stroke Investigators.

In: Annals of Neurology, Vol. 80, No. 2, 01.08.2016, p. 211-218.

Research output: Contribution to journalArticle

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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.",
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AU - for the Wake-Up Stroke Investigators

AU - Barreto, Andrew D.

AU - Fanale, Christopher V.

AU - Alexandrov, Andrei

AU - Gaffney, Kevin C.

AU - Vahidy, Farhaan S.

AU - Nguyen, Claude B.

AU - Sarraj, Amrou

AU - Rahbar, Mohammad

AU - Grotta, James C.

AU - Savitz, Sean I.

AU - Sands, Kara A.

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AU - Navalkele, Digvijaya D.

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