학술논문
Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial
Document Type
Academic Journal
Author
Koga, Masatoshi; Yamamoto, Haruko; Inoue, Manabu; Asakura, Koko; Aoki, Junya; Hamasaki, Toshimitsu; Kanzawa, Takao; Kondo, Rei; Ohtaki, Masafumi; Itabashi, Ryo; Kamiyama, Kenji; Iwama, Toru; Nakase, Taizen; Yakushiji, Yusuke; Igarashi, Shuichi; Nagakane, Yoshinari; Takizawa, Shunya; Okada, Yasushi; Doijiri, Ryosuke; Tsujino, Akira; Ito, Yasuhiro; Ohnishi, Hideyuki; Inoue, Takeshi; Takagi, Yasushi; Hasegawa, Yasuhiro; Shiokawa, Yoshiaki; Sakai, Nobuyuki; Osaki, Masato; Uesaka, Yoshikazu; Yoshimura, Shinichi; Urabe, Takao; Ueda, Toshihiro; Ihara, Masafumi; Kitazono, Takanari; Sasaki, Makoto; Oita, Akira; Yoshimura, Sohei; Fukuda-Doi, Mayumi; Miwa, Kaori; Kimura, Kazumi; Minematsu, Kazuo; Toyoda, Kazunori
Source
Stroke. May 01, 2020 51(5):1530-1538
Subject
Language
English
ISSN
0039-2499
Abstract
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. REGISTRATION—: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.