Abstract

Background

Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited.

Methods

In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death.

Results

A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P=0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively.

Conclusions

In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.)

요약

• 소개 : Tenecteplase는 뇌졸중 발병 후 4.5시간 이내에 치료를 받는 환자에게 효과적인 혈전 용해제이다. 하지만 Tenecteplase에 대한 뇌졸중 발병 4.5시간 이후의 효과는 아직 확립되지 않았다.

  본 연구는 중국에서 실시된 임상시험으로, 대혈관 경색이 발생한 환자들을 대상으로 뇌졸중 발생 이후 치료 시점별 Tenecteplase의 효과를 확인하기 위한 연구이다.

  
  

• 방법 : 대혈관 경색이 발생한 환자들 중 혈관경유 혈전제거술을 받을 수 없는 환자들을 무작위 배정하여 뇌졸중 발생 4.5시간에서 24시간 사이에 Tenecteplase 또는 표준치료인(항혈소판제)를 투여하였다.

  
  

• 결과 1) Tenecteplase를 투여받은 그룹이 표준치료 그룹에 비해 치료 90일 후의 mRS 점수가 높았다. 2) 치료 90일 후 사망률은 Tenecteplase 그룹과 표준치료 그룹이 각각 13.3%, 13.1%로 비슷했다. 3) 치료 36시간 이내에 발생한 증상이 있는 두개내 출혈의 발생률은 Tenecteplase 그룹과 표준치료 그룹이 각각 3.0%, 0.8%로 Tenecteplase 그룹이 더 높았다.

  
  

• 결론 : 대혈관 경색으로 인한 허혈성 뇌졸중 발생 4.5시간 초과 24시간 이내 환자들에게 Tenecteplase를 투여하는 것은 표준치료에 비해 신경학적 장애 발생 비율이 적고, 생존율은 비슷하지만, 증상이 있는 두개내 출혈의 발생 확률이 더 높다.