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Original research
Thrombolysis with alteplase 3–4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China
  1. Huaguang Zheng1,2,
  2. Yi Yang3,
  3. Huisheng Chen4,
  4. Chuanling Li5,
  5. Yangkun Chen6,
  6. Fu-Dong Shi7,
  7. Li Yang7,
  8. Xiaoping Cui8,
  9. Zuneng Lu9,
  10. Yanling Liang10,
  11. Songbiao Cui11,
  12. Anding Xu12,
  13. Yiqing Wu13,
  14. Yaqing Sun13,
  15. Yongjun Wang1,2
  1. 1 Department of Neurology, Beijing Tiantan Hospital, Affiliated Capital Medical University, Beijing, China
  2. 2 China National Clinical Research Center for Neurological Diseases, Beijing, China
  3. 3 Department of Neurology, The First Hospital of Jilin University, Changchun, China
  4. 4 Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China
  5. 5 Department of Neurology, Xuzhou Central Hospital, Xuzhou, China
  6. 6 Neurology, Dongguan People's Hospital, Dongguan, China
  7. 7 Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
  8. 8 Department of Neurology, No.900 Hospital of Joint Logistics Support Force, Fuzhou, China
  9. 9 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
  10. 10 Department of Neurology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  11. 11 Department of Neurology, Yanbian University Hospital, Yanji, China
  12. 12 Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China
  13. 13 Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai, China
  1. Correspondence to Dr Yongjun Wang; yongjunwang{at}ncrcnd.org.cn

Abstract

Background and purpose Data on the efficacy and safety of alteplase for acute ischaemic stroke (AIS) administered 3–4.5 hours after the onset of stroke symptoms in Chinese patients is limited. We sought to determine whether AIS patients would benefit from thrombolysis with alteplase between 3 and 4.5 hours after the onset of stroke symptoms in a prospective, multicentre, single-arm trial in China.

Materials and methods Eligible AIS patients were given 0.9 mg/kg alteplase intravenously. The primary efficacy endpoint was a favourable outcome at 3 months, defined as a score of 0 or 1 on the modified Rankin Scale. Thresholds for the primary efficacy endpoint were determined to be 40% based on the literature review. The primary safety endpoint was symptomatic intracranial haemorrhage (sICH) according to the European Cooperative Acute Stroke Study III (ECASS III) trial definition. Post hoc analysis between this study and the ECASS III trial were compared using the propensity score matching (PSM) method.

Results A total of 120 eligible AIS patients from 11 sites in China received thrombolysis therapy in this study. The median time from onset of symptoms to needle was 3 hours 54 min. The percentage of patients with a favourable outcome was 63.3% (95% CI 54.4 to 71.4), significantly higher than the predefined threshold (p<0.0001). Three patients (2.5%, 95% CI 0.5 to 7.1) had sICH, including two fatal sICH. Six patients died within 3 months after treatment. The post hoc PSM analysis showed a numerically higher rate of the primary efficacy endpoint in this study (63.3%) than the matched placebo arm (56.7%) in the ECASS III trial.

Conclusions Intravenous alteplase with a standard dose administered between 3 and 4.5 hours after onset of symptoms is effective and safe for Chinese AIS patients.

Trial registration number NCT02930837

  • Stroke
  • thrombolysis
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/svn-2020-000337

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    Footnotes

    • Contributors HZ: conception and study design, analysis of data, data acquisition, drafted the manuscript for intellectual content; YY, HC, CL, YC, F-DS, LY, XC, ZL, YL, SC and AX: data acquisition, revised manuscript for intellectual content; YQW: study design, analysis of data, revised manuscript for intellectual content; YS: study design, statistical analysis of data, revised manuscript for intellectual content; YJW: conception and study design, analysis of data, revised manuscript for intellectual content. All authors have approved the manuscript to be published. The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group and its Licensees to permit this article (if accepted) to be published in Stroke and Vascular Neurology editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence.

    • Funding The study was funded by Boehringer Ingelheim (China) Investment. The study was also funded by Clinical Research with Features for Application in the Capital (no. Z161100000516079) and the National Key Research and Development Plan (no.2017YFC1308204).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request. To ensure independent interpretation of clinical study results, Boehringer Ingelheim granted all external authors access to all relevant material, including participant-level clinical study data, and relevant material as needed by them to fulfill their role and obligations as authors under the ICMJE criteria. Detailed requirement is provided in online supplementary material.