Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke

Importance: Although recent trials have shown benefit with early tirofiban after thrombolysis, its efficacy remains uncertain in patients with acute ischemic stroke who do not have a large or medium vessel occlusion or a cardioembolic source and who show an inadequate clinical response to intravenous tenecteplase. Objective: To assess the efficacy and safety of intravenous tirofiban administered after an inadequate response to intravenous tenecteplase in this specific patient population. Design, Setting, and Participants: Investigator-initiated, randomized, double-blind, placebo-controlled trial conducted at 37 hospitals in China, enrolling 359 patients with acute ischemic stroke, without large or medium vessel occlusion or cardioembolic etiology, and with an insufficient clinical response to intravenous tenecteplase (defined as no significant change from baseline, neurological deterioration, or neurological fluctuation based on serial assessment of the National Institutes of Health Stroke Scale score within 4-24 hours after infusion). Recruitment took place between April 24, 2024, and July 16, 2025, with final follow-up on October 11, 2025. Interventions: Intravenous tirofiban (n = 177), administered as a 0.3-μg/kg/min bolus over 30 minutes, followed by a continuous infusion of 0.075 μg/kg/min for up to 47.5 hours, or matching placebo (n = 182), initiated within 4 to 24 hours after intravenous tenecteplase. Oral antiplatelet therapy (aspirin and/or clopidogrel) was started 24 hours after thrombolysis in the placebo group and 44 hours after thrombolysis in the tirofiban group and continued in all patients through 90-day follow-up. Main Outcomes and Measures: The primary outcome was an excellent outcome (defined as a score of 0 or 1 on the modified Rankin Scale; range, 0-6, with higher scores indicating more severe disability) at 90 days. Safety outcomes included incidence of symptomatic intracranial hemorrhage within 48 hours and 90-day mortality. Results: Among 359 patients randomized (mean age, 66 years; 141 females [39.3%]), 358 (99.7%) completed the trial. An excellent outcome at 90 days was observed in 113 patients (63.8%) in the tirofiban group and in 95 patients (52.2%) in the placebo group (risk ratio, 1.22; 95% CI, 1.02-1.46; P = .03). Symptomatic intracranial hemorrhage within 48 hours occurred in 1 patient (0.9%) in the tirofiban group and no patients in the placebo group; 90-day mortality was 0.6% and 1.6%, respectively. Conclusions and Relevance: Among patients with acute ischemic stroke without large or medium vessel occlusion or a cardioembolic source who had an inadequate clinical response to intravenous tenecteplase, adjunctive intravenous tirofiban increased the likelihood of an excellent outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT05604638.

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Journal
JAMA
Published
2026-05-08
DOI
https://doi.org/10.1001/jama.2026.5245
Primary Topic
Acute Ischemic Stroke Management
Type
article
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article

Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke

Zhaohui Lai, Jinchun Ye, Xiang Zeng, Cong Zhang et al.
JAMA
Acute Ischemic Stroke Management
article

Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke

Zhaohui Lai, Jinchun Ye, Xiang Zeng, Cong Zhang, Zhiyong Xie, Hongliang Zeng, Xunwei Lv, Tianmin Lai, Wei Sun, Shizhan Li, Guoyong Zeng, Xianghong Liu, Min Zhou, Hailong Xu, Junda Li, Weihua Hu, Deyan Kong, Yuanlu Liu, Genxiang Xiao, Zongliang Li, Huashi Liu, Donghuan Mei, Shanggui Yuan, Ruize Zhou, Fangqun Cheng, Yi Yin, Shuhua Xie, Xinbo Deng, Yan Shi, Zhongming Qiu, Jingjing Liu, Fan Zhang, Xiaoyu Guan, Mayank Goyal, Lei Chen, Chong Zheng, Hairong Hu, Götz Thomalla, Duolao Wang, Bin Liu, Jeffrey L. Saver, Limin Shen, Daojun Hong, Shuiping Liang, Guangxiong Yuan, Bin Chen, Suyue Pan, Chunying Li, Hongfei Sang, Vignan Yogendrakumar, Bo Wang, Johannes Kaesmacher, Dan Li, Mengjie Lu, Jian Zhang, Qingwu Yang, Yamei Tang, Wenfeng Cao, Yi Chen, Junfeng Shi, Baozhu Guan, Raul G. Nogueira, INSTANT Trial Authors for the INSTANT Investigators, Thanh N. Nguyen
article en

Abstract

Importance: Although recent trials have shown benefit with early tirofiban after thrombolysis, its efficacy remains uncertain in patients with acute ischemic stroke who do not have a large or medium vessel occlusion or a cardioembolic source and who show an inadequate clinical response to intravenous tenecteplase. Objective: To assess the efficacy and safety of intravenous tirofiban administered after an inadequate response to intravenous tenecteplase in this specific patient population. Design, Setting, and Participants: Investigator-initiated, randomized, double-blind, placebo-controlled trial conducted at 37 hospitals in China, enrolling 359 patients with acute ischemic stroke, without large or medium vessel occlusion or cardioembolic etiology, and with an insufficient clinical response to intravenous tenecteplase (defined as no significant change from baseline, neurological deterioration, or neurological fluctuation based on serial assessment of the National Institutes of Health Stroke Scale score within 4-24 hours after infusion). Recruitment took place between April 24, 2024, and July 16, 2025, with final follow-up on October 11, 2025. Interventions: Intravenous tirofiban (n = 177), administered as a 0.3-μg/kg/min bolus over 30 minutes, followed by a continuous infusion of 0.075 μg/kg/min for up to 47.5 hours, or matching placebo (n = 182), initiated within 4 to 24 hours after intravenous tenecteplase. Oral antiplatelet therapy (aspirin and/or clopidogrel) was started 24 hours after thrombolysis in the placebo group and 44 hours after thrombolysis in the tirofiban group and continued in all patients through 90-day follow-up. Main Outcomes and Measures: The primary outcome was an excellent outcome (defined as a score of 0 or 1 on the modified Rankin Scale; range, 0-6, with higher scores indicating more severe disability) at 90 days. Safety outcomes included incidence of symptomatic intracranial hemorrhage within 48 hours and 90-day mortality. Results: Among 359 patients randomized (mean age, 66 years; 141 females [39.3%]), 358 (99.7%) completed the trial. An excellent outcome at 90 days was observed in 113 patients (63.8%) in the tirofiban group and in 95 patients (52.2%) in the placebo group (risk ratio, 1.22; 95% CI, 1.02-1.46; P = .03). Symptomatic intracranial hemorrhage within 48 hours occurred in 1 patient (0.9%) in the tirofiban group and no patients in the placebo group; 90-day mortality was 0.6% and 1.6%, respectively. Conclusions and Relevance: Among patients with acute ischemic stroke without large or medium vessel occlusion or a cardioembolic source who had an inadequate clinical response to intravenous tenecteplase, adjunctive intravenous tirofiban increased the likelihood of an excellent outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT05604638.

JAMA
Ningbo University (CN), Hebei Medical University (CN), University of Bern (CH), Huaihua University (CN), Boston Medical Center (US), Fujian Medical University (CN), The Royal Melbourne Hospital (AU), Nanchang University (CN), Army Medical University (CN), Sun Yat-sen University (CN), Universität Hamburg (DE), Guangxi Medical University (CN), University of California, Los Angeles (US), The University of Melbourne (AU), Hunan University (CN), University of Calgary (CA), Xuzhou Medical College (CN), Liverpool School of Tropical Medicine (GB), Yichun University (CN), Ottawa Hospital (CA), Shatin Hospital (CN), University Hospital of Bern (CH), Ruijin Hospital (CN), South County Hospital (US), Westlake University (CN), Ningbo University of Finance & Economics (CN), Xian Central Hospital (CN), Ganzhou People's Hospital (CN), Sun Yat-sen Memorial Hospital (CN), Linyi People's Hospital (CN), UPMC Health System (US), Nanfang Hospital (CN), Second Hospital of Yichang (CN), Jiangxi Provincial People's Hospital (CN), University Medical Center Hamburg-Eppendorf (DE), Xingtai People's Hospital (CN), Xinqiao Hospital (CN), Xiangyang Central Hospital (CN), Zoucheng People's Hospital (CN), The 180th Hospital of PLA (CN), First Affiliated Hospital of Fujian Medical University (CN), Shengli Oilfield Central Hospital (CN), Xintai People's Hospital (CN), Xinjiang Uygur Autonomous Region Uygur Medicine Hospital (CN), University of Pittsburgh Medical Center (US), Xuzhou No.1 People's Hospital (CN), Klinik und Poliklinik für Neurologie (DE), Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN), Qujiang People's Hospital (CN), Shangluo Central Hospital (CN), Tang Hospital (CN), Daye People's Hospital (CN), Huangshi Central Hospital (CN), Yulin University (CN), Yuxian People's Hospital (CN), Southern Medical University (CN)
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