Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Shuya, Pan, Yuesong, Wang, Ziran, Liang, Zhigang, Chen, Huisheng, Wang, Dong, Sui, Yi, Zhao, Xingquan, Wang, Yilong, Du, WanLiang, Zheng, Huaguang, Wang, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
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
_version_ 1784663957635596288
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
work_keys_str_mv AT lishuya safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT panyuesong safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT wangziran safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT liangzhigang safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT chenhuisheng safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT wangdong safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT suiyi safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT zhaoxingquan safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT wangyilong safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT duwanliang safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT zhenghuaguang safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy
AT wangyongjun safetyandefficacyoftenecteplaseversusalteplaseinpatientswithacuteischaemicstroketraceamulticentrerandomisedopenlabelblindedendpointprobecontrolledphaseiistudy