Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study

Background Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. Methods This is a...

Full description

Saved in:
Bibliographic Details
Main Authors: Xia Meng, Shuya Li, Hongguo Dai, Guozhi Lu, Weiwei Wang, Fengyuan Che, Yu Geng, Minghui Sun, Xiyan Li, Yongjun Wang
Format: Article
Language:English
Published: Wiley 2024-07-01
Series:Stroke: Vascular and Interventional Neurology
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/SVIN.124.001363
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849734499036823552
author Xia Meng
Shuya Li
Hongguo Dai
Guozhi Lu
Weiwei Wang
Fengyuan Che
Yu Geng
Minghui Sun
Xiyan Li
Yongjun Wang
author_facet Xia Meng
Shuya Li
Hongguo Dai
Guozhi Lu
Weiwei Wang
Fengyuan Che
Yu Geng
Minghui Sun
Xiyan Li
Yongjun Wang
author_sort Xia Meng
collection DOAJ
description Background Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. Methods This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China. Results The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90. Conclusions It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China. Clinical Trial Registration Information NCT04915729 (https://clinicaltrials.gov/study/NCT04915729)
format Article
id doaj-art-a65a6abe728045b8a7dc4c4b97cd4d97
institution DOAJ
issn 2694-5746
language English
publishDate 2024-07-01
publisher Wiley
record_format Article
series Stroke: Vascular and Interventional Neurology
spelling doaj-art-a65a6abe728045b8a7dc4c4b97cd4d972025-08-20T03:07:46ZengWileyStroke: Vascular and Interventional Neurology2694-57462024-07-014410.1161/SVIN.124.001363Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL StudyXia Meng0Shuya Li1Hongguo Dai2Guozhi Lu3Weiwei Wang4Fengyuan Che5Yu Geng6Minghui Sun7Xiyan Li8Yongjun Wang9Department of Neurology and Department of Clinical Trial Center Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurology and Department of Clinical Trial Center Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Emergency Linfen Central Hospital Linfen ChinaDepartment of Neurology Hexigten Banner Mongolian Traditional Chinese Medicine Hospital Chifeng ChinaDepartment of Neurology Xianyang Hospital of Yan'an University Xianyang ChinaDepartment of Neurology Linyi People's Hospital Linyi ChinaCenter for Rehabilitation Medicine, Department of Neurology Zhejiang Provincial People's Hospital Hangzhou ChinaBoehringer Ingelheim (China) Investment Co., Ltd Shanghai ChinaBoehringer Ingelheim (China) Investment Co., Ltd Shanghai ChinaDepartment of Neurology and Department of Clinical Trial Center Beijing Tiantan Hospital, Capital Medical University Beijing ChinaBackground Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. Methods This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China. Results The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90. Conclusions It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China. Clinical Trial Registration Information NCT04915729 (https://clinicaltrials.gov/study/NCT04915729)https://www.ahajournals.org/doi/10.1161/SVIN.124.001363alteplaseChinesefunctional outcomeischemic strokesymptomatic intracerebral hemorrhagetenecteplase
spellingShingle Xia Meng
Shuya Li
Hongguo Dai
Guozhi Lu
Weiwei Wang
Fengyuan Che
Yu Geng
Minghui Sun
Xiyan Li
Yongjun Wang
Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
Stroke: Vascular and Interventional Neurology
alteplase
Chinese
functional outcome
ischemic stroke
symptomatic intracerebral hemorrhage
tenecteplase
title Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
title_full Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
title_fullStr Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
title_full_unstemmed Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
title_short Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
title_sort tenecteplase versus alteplase in acute ischemic stroke in chinese patients protocol for the original study
topic alteplase
Chinese
functional outcome
ischemic stroke
symptomatic intracerebral hemorrhage
tenecteplase
url https://www.ahajournals.org/doi/10.1161/SVIN.124.001363
work_keys_str_mv AT xiameng tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT shuyali tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT hongguodai tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT guozhilu tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT weiweiwang tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT fengyuanche tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT yugeng tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT minghuisun tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT xiyanli tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy
AT yongjunwang tenecteplaseversusalteplaseinacuteischemicstrokeinchinesepatientsprotocolfortheoriginalstudy