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Randomized Controlled Trial
. 2020 May;51(5):1530-1538.
doi: 10.1161/STROKEAHA.119.028127. Epub 2020 Apr 6.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial

Masatoshi Koga  1 , Haruko Yamamoto  2 , Manabu Inoue  1 , Koko Asakura  3 , Junya Aoki  4 , Toshimitsu Hamasaki  3 , Takao Kanzawa  5 , Rei Kondo  6 , Masafumi Ohtaki  7 , Ryo Itabashi  8 , Kenji Kamiyama  9 , Toru Iwama  10 , Taizen Nakase  11   12 , Yusuke Yakushiji  13 , Shuichi Igarashi  14 , Yoshinari Nagakane  15 , Shunya Takizawa  16 , Yasushi Okada  17 , Ryosuke Doijiri  18 , Akira Tsujino  19 , Yasuhiro Ito  20 , Hideyuki Ohnishi  21 , Takeshi Inoue  22 , Yasushi Takagi  23 , Yasuhiro Hasegawa  24 , Yoshiaki Shiokawa  25 , Nobuyuki Sakai  26 , Masato Osaki  27 , Yoshikazu Uesaka  28 , Shinichi Yoshimura  29 , Takao Urabe  30 , Toshihiro Ueda  31 , Masafumi Ihara  32 , Takanari Kitazono  33 , Makoto Sasaki  34 , Akira Oita  35 , Sohei Yoshimura  1 , Mayumi Fukuda-Doi  1   3 , Kaori Miwa  1 , Kazumi Kimura  4 , Kazuo Minematsu  1   36 , Kazunori Toyoda  1 ; THAWS Trial Investigators
Affiliations
Randomized Controlled Trial

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial

Masatoshi Koga et al. Stroke. 2020 May.

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.

Keywords: control groups; informed consent; intracranial hemorrhages; magnetic resonance imaging; stroke, acute; tissue-type plasminogen activator.

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Figures

Figure 1.
Figure 1.
Screening and randomization of patients. FLAIR indicates fluid-attenuated inversion recovery.
Figure 2.
Figure 2.
Distribution of scores on 90-d modified Rankin Scale (intention-to-treat population).
Figure 3.
Figure 3.
Prespecified (A) and additional (B) subgroup analyses: relative risks and 95% CIs for favorable outcome. ASPECTS indicates Alberta Stroke Program Early CT Score; FLAIR, fluid-attenuated inversion recovery; MRA, magnetic resonance angiography; and NIHSS, National Institutes of Health Stroke Scale.
See this image and copyright information in PMC

References

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