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Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study
BACKGROUND: Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic strok...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899644/ https://www.ncbi.nlm.nih.gov/pubmed/34429364 http://dx.doi.org/10.1136/svn-2021-000978 |
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author | Li, Shuya Pan, Yuesong Wang, Ziran Liang, Zhigang Chen, Huisheng Wang, Dong Sui, Yi Zhao, Xingquan Wang, Yilong Du, WanLiang Zheng, Huaguang Wang, Yongjun |
author_facet | Li, Shuya Pan, Yuesong Wang, Ziran Liang, Zhigang Chen, Huisheng Wang, Dong Sui, Yi Zhao, Xingquan Wang, Yilong Du, WanLiang Zheng, Huaguang Wang, Yongjun |
author_sort | Li, Shuya |
collection | PubMed |
description | BACKGROUND: Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China. METHODS: This multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours. RESULTS: Between May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events. CONCLUSIONS: Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations. TRIAL REGISTRATION NUMBER: NCT04676659. |
format | Online Article Text |
id | pubmed-8899644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-88996442022-03-22 Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study Li, Shuya Pan, Yuesong Wang, Ziran Liang, Zhigang Chen, Huisheng Wang, Dong Sui, Yi Zhao, Xingquan Wang, Yilong Du, WanLiang Zheng, Huaguang Wang, Yongjun Stroke Vasc Neurol Original Research BACKGROUND: Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China. METHODS: This multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours. RESULTS: Between May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events. CONCLUSIONS: Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations. TRIAL REGISTRATION NUMBER: NCT04676659. BMJ Publishing Group 2021-08-24 /pmc/articles/PMC8899644/ /pubmed/34429364 http://dx.doi.org/10.1136/svn-2021-000978 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://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://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Li, Shuya Pan, Yuesong Wang, Ziran Liang, Zhigang Chen, Huisheng Wang, Dong Sui, Yi Zhao, Xingquan Wang, Yilong Du, WanLiang Zheng, Huaguang Wang, Yongjun Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title | Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title_full | Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title_fullStr | Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title_full_unstemmed | Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title_short | Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study |
title_sort | safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (trace): a multicentre, randomised, open label, blinded-endpoint (probe) controlled phase ii study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899644/ https://www.ncbi.nlm.nih.gov/pubmed/34429364 http://dx.doi.org/10.1136/svn-2021-000978 |
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