number of access : ?
number of downloads : ?
ID 115806
Title Alternative
Low-Dose Intravenous Alteplase in Wake-Up Stroke
Koga, Masatoshi National Cerebral and Cardiovascular Center
Yamamoto, Haruko National Cerebral and Cardiovascular Center
Inoue, Manabu National Cerebral and Cardiovascular Center
Asakura, Koko National Cerebral and Cardiovascular Center
Aoki, Junya Nippon Medical School
Hamasaki, Toshimitsu National Cerebral and Cardiovascular Center
Kanzawa, Takao Mihara Memorial Hospital
Kondo, Rei Yamagata City Hospital Saiseikan
Ohtaki, Masafumi Obihiro Kosei Hospital
Itabashi, Ryo Kohnan Hospital
Kamiyama, Kenji Nakamura Memorial Hospital
Iwama, Toru Gifu University
Nakase, Taizen Research Institute for Brain and Blood Vessels|Akita University
Yakushiji, Yusuke Saga University
Igarashi, Shuichi Niigata City General Hospital
Nagakane, Yoshinari Kyoto Second Red Cross Hospital
Takizawa, Shunya Tokai University
Okada, Yasushi National Hospital Organization Kyushu Medical Center
Doijiri, Ryosuke Iwate Prefectural Central Hospital
Tsujino, Akira Nagasaki University
Ito, Yasuhiro Toyota Memorial Hospital
Ohnishi, Hideyuki Ohnishi Neurological Center
Inoue, Takeshi Kawasaki Medical School
Hasegawa, Yasuhiro St. Marianna University School of Medicine
Shiokawa, Yoshiaki Kyorin University
Sakai, Nobuyuki Kobe City Medical Center General Hospital
Osaki, Masato Steel Memorial Yawata Hospital
Uesaka, Yoshikazu Toranomon Hospital
Yoshimura, Shinichi Hyogo College of Medicine
Urabe, Takao Juntendo University
Ueda, Toshihiro St. Marianna University
Ihara, Masafumi National Cerebral and Cardiovascular Center
Kitazono, Takanari Kyushu University
Sasaki, Makoto Iwate Medical University
Oita, Akira National Cerebral and Cardiovascular Center
Yoshimura, Sohei National Cerebral and Cardiovascular Center
Fukuda-Doi, Mayumi National Cerebral and Cardiovascular Center
Miwa, Kaori National Cerebral and Cardiovascular Center
Kimura, Kazumi Nippon Medical School
Minematsu, Kazuo National Cerebral and Cardiovascular Center|Iseikai Medical Corporation
Toyoda, Kazunori National Cerebral and Cardiovascular Center
control groups
informed consent
intracranial hemorrhages
magnetic resonance imaging
stroke, acute
tissue-type plasminogen activator
Content Type
Journal Article
Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset.
Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1).
Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively.
Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions.
Journal Title
American Heart Association|Wolters Kluwer Health
Start Page
End Page
Published Date
This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License(, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
DOI (Published Version)
URL ( Publisher's Version )
FullText File
Medical Sciences