Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study Protocol and Rationale

Bin Yang; Xuesong Bai; Ting-Yu Yi; Haibo Wang; Yifeng Liu; Lin Ma; Sheng Liu; Shaoguang Wu; Liyong Zhang; Ya Peng; Raul Nogueira; Wenhuo Chen; Liqun Jiao

doi:10.1177/17474930251313940

Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study Protocol and Rationale

Int J Stroke. 2025 Jan 4:17474930251313940. doi: 10.1177/17474930251313940. Online ahead of print.

Authors

Bin Yang¹, Xuesong Bai¹, Ting-Yu Yi², Haibo Wang³, Yifeng Liu⁴, Lin Ma⁵, Sheng Liu⁶, Shaoguang Wu⁷, Liyong Zhang⁸, Ya Peng⁹, Raul Nogueira¹⁰, Wenhuo Chen¹¹, Liqun Jiao¹²

Affiliations

¹ Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, 45 Changchun St, Beijing 100053, China.
² Department of Neurointervention, Zhangzhou Municipal Hospital, No. 9 Zhangma Road, Yancuo Town, Longhai District, Zhangzhou 363100, China.
³ Peking University Clinical Research Institute, Peking University First Hospital, 38 Xueyuan St, Beijing 100191, China.
⁴ Department of Neurology, Nanyang Central Hospital, No. 312 Gongnong Road, Wancheng District, Nanyang City, Henan 473005, China.
⁵ Department of Neurosurgery, Huanhu Hospital, No. 6 Jizhao Road, Jinnan District, Tianjin, 300060, China.
⁶ Department of Interventional Radiology, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu 210029, China.
⁷ Department of Neurosurgery, Gaomi People's Hospital, 77, Zhenfu St, Gaomi, Weifang City, Shandong 261500, China.
⁸ Department of Neurosurgery, Liaocheng People's Hospital, No. 45 Huashan Road, Liaocheng Economic Development Zone, Liaocheng Shandong 252000, China.
⁹ Department of Neurosurgery, The First People's Hospital of Changzhou, No. 185, Guqian Street, Tianning District, Changzhou, 213000, China.
¹⁰ University of Pittsburgh Medical Center Stroke Institute, Department of Neurology and Neurosurgery, University of Pittsburgh School of Medicine, PUH C-400, 200 Lothrop Street, PA 15213.
¹¹ Department of Cerebrovascular Disease, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian, China.
¹² Department of Neurosurgery and Interventional Neuroradiology, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, 45 Changchun St, Beijing 100053, China.

PMID: 39754489
DOI: 10.1177/17474930251313940

Abstract

Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Sample size: To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) have completed 90-day follow-up.

Methods and design: The IAT-TOP trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] 2b ≥50).

Study outcomes: The primary outcome is the modified Rankin Scale (mRS) score of 0-2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0-3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 hours, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 hours and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 hours, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events.

Discussion: The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy.

Trial registration: ClinicalTrials.gov NCT05897554.

Keywords: Acute stroke therapy; Asia; Cerebral Infarction; Clinical trial; Developing countries; Ischaemic stroke.

Associated data

ClinicalTrials.gov/NCT05897554