Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial

Shuya Li; Runqi Wangqin; Yuesong Pan; Aoming Jin; Hao Li; Lee H Schwamm; Marc Fisher; Bruce C V Campbell; Mark W Parsons; Ziran Wang; Hongguo Dai; Deyang Li; Runhui Li; Junhai Wang; David Wang; Yilong Wang; Xingquan Zhao; Zixiao Li; Huaguang Zheng; Yunyun Xiong; Xia Meng; Yongjun Wang

doi:10.1136/svn-2023-002694

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial

Stroke Vasc Neurol. 2024 Jan 31:svn-2023-002694. doi: 10.1136/svn-2023-002694. Online ahead of print.

Authors

Shuya Li^{1

2

3}, Runqi Wangqin⁴, Yuesong Pan^{1

2

3}, Aoming Jin^{1

2

3}, Hao Li^{1

2

3}, Lee H Schwamm⁵, Marc Fisher⁶, Bruce C V Campbell⁷, Mark W Parsons⁸, Ziran Wang⁹, Hongguo Dai¹⁰, Deyang Li¹¹, Runhui Li¹², Junhai Wang¹³, David Wang¹⁴, Yilong Wang^{1

2

3}, Xingquan Zhao^{1

2

3}, Zixiao Li^{1

2

3}, Huaguang Zheng^{1

2

3}, Yunyun Xiong^{1

2

3}, Xia Meng^{1

2

3}, Yongjun Wang^{15

2

3}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing, China.
³ Department of Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Department of Neurology, Duke University Medical Center, Durham, NC, USA.
⁵ Department of Neurology and Comprehensive Stroke Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁷ Department of Medicine and Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Department of Neurology, Liverpool Hospital, University of New South Wales South Western Sydney Clinical School, Sydney, New South Wales, Australia.
⁹ Department of Neurology, Linyi People's Hospital, Linyi, Shandong, China.
¹⁰ Department of Neurology, Linfen Central Hospital, Linfen, China.
¹¹ Department of Neurology, Tengzhou Central People's Hospital, Tengzhou, Shandong, China.
¹² Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.
¹³ Department of Neurology, General Hospital of DaTong Coal Mine Group, Datong, Shanxi, China.
¹⁴ Department of Neurology, Petznick Stroke Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
¹⁵ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China yongjunwang@ncrcnd.org.cn.

PMID: 38296586
DOI: 10.1136/svn-2023-002694

Abstract

Background: The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.

Methods: This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.

Results: Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min.

Conclusions: In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Keywords: Clinical Trial; Ischemic Attack, Transient; Stroke; Thrombolysis.