A pilot study of a new thrombolytic agent for acute ischemic stroke in Taiwan within a five-hour window.
OBJECTIVE
This study was the first clinical trial in Taiwan of a new thrombolytic agent human tissue urokinase type plasminogen activator (HTUPA) in patients with acute ischemic stroke.


METHODS
Patients were treated with a single bolus intravenous HTUPA under an open-label dose escalation design within 5 hours after symptom onset. Safety outcomes were assessed by symptomatic and asymptomatic intracerebral hemorrhage (ICH) as well as other bleeding episodes. Preliminary efficacy was measured by National Institutes of Health Stroke Scale (NIHSS).


RESULTS
Three doses of HTUPA (0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg) were administered to 33 patients, with the majority of patients (n=29) receiving 0.3 mg/kg. Two cases of fatal ICH occurred: 1 in the patient who received 0.4 mg/kg and the other in the 0.3 mg/kg group. Asymptomatic ICH occurred in 6 patients. Other treatment-related serious adverse events were ecchymosis, hematuria, and upper gastrointestinal bleeding, which were completely recovered. At day 90, in patients treated with 0.3 mg/kg within a 0- to 5-hour window, 34% reached NIHSS scores 0 to 1, whereas of those treated within 0 to 3 hours, 86% reached this score.


CONCLUSIONS
Intravenous HTUPA, given at 0.3 mg/kg as a bolus injection within 5 hours after symptom onset, had an acceptable safety and efficacious profile in patients with acute ischemic stroke.
Hu
Han-Hwa
HH
Department of Neurology, Taipei Veterans General Hospital, Taiwan. hhhu@vghtpe.gov.tw
Teng
Michael Mu-Huo
MM
Hsu
Li-Chi
LC
Wong
Wen-Jang
WJ
Wang
Lee-Min
LM
Luk
Yun-On
YO
Chern
Chang-Ming
CM
Soong
Bing-Wen
BW
Sheng
Wen-Yung
WY
D000368:Aged; D002545:Brain Ischemia / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D013624:Taiwan; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator