Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke (INSTANT)

Safety and Efficacy of Early Administration of Tirofiban in Patients Treated With Tenecteplase for Acute Ischemic Stroke

The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Tirofiban Hydrochloride; Drug: Placebo

Detailed Description

Intravenous thrombolysis with alteplase is recommended in treatment guidelines for patients with acute ischemic stroke. Previous studies showed that intravenous tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischemic stroke who meet standard criteria for thrombolysis. After thrombolysis-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after intravenous thrombolysis could reduce the risk of reocclusion and improve outcome. The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.

• Study Type: Interventional
• Enrollment (Estimated): 348
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Deyan Kong, MD; Phone Number: +8618376635080; Email: kongdeyangxnn@163.com
• Study Contact Backup: Name: Guoyong Zeng, MD; Phone Number: +8613507079530; Email: hsyygy@163.com

Study Locations

• China
  • Anhui
    • Chuzhou, Anhui, China
      • Recruiting
      • Mingguang People's Hospital
      • Contact: Lei Chen
      • Contact: Zongliang Li,
  • Fujian
    • Longyan, Fujian, China
      • Recruiting
      • Longyan People´s Hospital, Longyan City
      • Contact: Yuqin Deng
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • The Second Affiliated Hospital of Guangxi Medical University
      • Contact: Deyan Kong, MD
  • Hubei
    • Huanggang, Hubei, China
      • Recruiting
      • Huangmei People's Hospital
      • Contact: Junfeng Shi
      • Contact: Hongtao Huo
    • Yichang, Hubei, China
      • Recruiting
      • Yiling People's Hospital of Yichang city
      • Contact: Hailong Xu
      • Contact: Zhenxing Liu
  • Hunan
    • Huaihua, Hunan, China
      • Recruiting
      • Hunan Xupu Chengnan Hospital
      • Contact: Bin Zhang
      • Contact: Bo Wang
    • Shaoyang, Hunan, China
      • Recruiting
      • People's Hospital Of Shaodong
      • Contact: Limin Shen
    • Xiangtan, Hunan, China
      • Recruiting
      • Shaoshan People's Hospital
      • Contact: Zhenhua Xiao
      • Contact: Shuai Zhao
    • Xiangtan, Hunan, China
      • Recruiting
      • Xiangtan Central Hospitall
      • Contact: Guangxiong Yuan
      • Contact: Junxiong Wu
    • Yueyang, Hunan, China
      • Recruiting
      • Hunan University of Medicine Affiliated Pingjiang Hospital
      • Contact: Xiang Zeng
      • Contact: Sire Li
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • Ganzhou People's Hospital
      • Contact: Guoyong Zeng, MD; Phone Number: +8613507079530; Email: hsyygy@163.com
      • Contact: Fan Zhang; Phone Number: +8618970148470
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Dayu County
      • Contact: Huashi Liu,
      • Contact: Yongfang Deng
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Ganxian District
      • Contact: Weihua Hu,
      • Contact: Jianyong Chen
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Quannan County
      • Contact: Qiang Li
      • Contact: Bin Chen
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of RuiJin City
      • Contact: Ruize Zhou
      • Contact: Xiaomei Lai
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Shangyou County
      • Contact: Yi Yin
      • Contact: Daofei Liu
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Xinfeng County
      • Contact: Yan Shi
      • Contact: Qing Chen
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Xunwu County
      • Contact: Donghuan Mei
      • Contact: Hailin Yan
    • Ganzhou, Jiangxi, China, 341000
      • Recruiting
      • People's Hospital of Yudu County
      • Contact: Zhiyong Xie,
      • Contact: Qingfeng Zeng
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Ganzhou Municipal Hospital
      • Contact: Hongwen Liu
      • Contact: Jiangqiang Lai
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Nankang TCM Hospital
      • Contact: Fangwei Li
      • Contact: Long Gao
    • Ganzhou, Jiangxi, China
      • Recruiting
      • People's Hospital of Anyuan County
      • Contact: Hong Zhang
      • Contact: Xiaobin Zeng
    • Ganzhou, Jiangxi, China
      • Recruiting
      • People's Hospital of Chongyi County
      • Contact: Xunwei Lv,
      • Contact: Huadong Li
    • Ganzhou, Jiangxi, China
      • Recruiting
      • People's Hospital of Shicheng County
      • Contact: Gengxiang Xiao
      • Contact: Longshen Huang
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Second Hospital of Xingguo County
      • Contact: Shanggui Yuan
      • Contact: Yanmao Liu
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Second People's Hospital of Yudu County
      • Contact: Xiaoyu Guan,
      • Contact: Luyang Wang
    • Ganzhou, Jiangxi, China
      • Recruiting
      • The People's Hospital of Ningdu County
      • Contact: Jian Xiao
      • Contact: Hairong Hu,
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Traditional Chinese Medicine Hospital of Xingguo County
      • Contact: Shuiping Liang
      • Contact: Xiankun Yang
    • Ganzhou, Jiangxi, China
      • Recruiting
      • Traditional Chinese Medicine Hospital of Yudu County
      • Contact: Jinchang Tan
      • Contact: Guozhen Liu
    • Jiujiang, Jiangxi, China
      • Recruiting
      • Affiliated Hospital of Jiujiang University
      • Contact: Zhongbin Xia
      • Contact: Ye Liu
    • Ji’an, Jiangxi, China
      • Recruiting
      • Ji'an Central People's Hospital
      • Contact: Yi Chen
    • Ji’an, Jiangxi, China
      • Recruiting
      • People's Hospital of Wan'an county
      • Contact: Bin Liu
      • Contact: Wenbin Qiu
    • Nanchang, Jiangxi, China
      • Recruiting
      • Jiangxi Provincial People's Hospital
      • Contact: Wenfeng Cao
      • Contact: Zhengbing Xiang
    • Yichun, Jiangxi, China
      • Recruiting
      • People's Hospital of Yichun
      • Contact: Ling Gao
      • Contact: Xinbo Deng
    • Yingtan, Jiangxi, China
      • Recruiting
      • Yingtan People's Hospital
      • Contact: Jingjing Liu
      • Contact: Tianpei Li
  • Jilin
    • Songyuan, Jilin, China
      • Recruiting
      • Songyuan Jilin Oilfield Hospital
      • Contact: Ying Jin
      • Contact: Chunying Li
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • Dalian Municipal Central Hospital
      • Contact: Zhongjun Chen
      • Contact: Manhong zhao
  • Neimenggu
    • Chifeng, Neimenggu, China
      • Recruiting
      • Zhongmeng Hospital of Hexigten Banner
      • Contact: Dan Li
      • Contact: Guozhi Lu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old;
2. Within 4-24 hours after intravenous thrombolytic therapy with tenerplase for acute ischemic stroke, there was no significant change in symptoms compared to the baseline (defined as an increase or decrease of 0 or 1 point in the NIHSS score), and neurological function deteriorated (defined as an increase of ≥ 2 in the NIHSS score compared to the baseline) Fluctuations in neurological function (defined as an increase of 4 points or more in the NIHSS score compared to the baseline and then a decrease of 4 points or more);
3. NIHSS ≥ 4 points before randomization;
4. The patient or their family members sign a written informed consent form.

Exclusion Criteria:

1. Intracranial hemorrhage was confirmed by CT or MRI after intravenous thrombolysis and before randomization;
2. CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1, M2 or M3 segment, anterior cerebral artery A1, A2 or A3 segment, posterior cerebral artery P1, P2 or P3, vertebral or basilar artery;
3. Confirmed or suspected cardioembolic stroke mechanisms, including any of the following: documented cardiac sources of thromboembolism: chronic or paroxysmal atrial fibrillation, rheumatic mitral stenosis, prosthetic heart valves, infective endocarditis, intracardiac thrombus or implanted prosthetic material, dilated cardiomyopathy (left ventricular ejection fraction <40%), or spontaneous echo contrast in the left atrium; other laboratory-confirmed embolic sources: patent foramen ovale with concomitant atrial septal aneurysm, or cryptogenic stroke with a CHADS-VASC score ≥ 2 indicating high thromboembolic risk;
4. Blood platelet count was lower than 100×10^9/L;
5. Renal insufficiency, glomerular filtration rate < 30 mL/min;
6. Pregnant or lactating women;
7. Allergic to tirofiban, nickel, titanium or their alloys;
8. Prior neurological or psychiatric illness that prevents assessment of neurological function;
9. Pre-existing bleeding disease, severe heart, liver, or kidney disease, or sepsis;
10. Brain tumors with a space-occupying effect on imaging (other than micromeningiomas);
11. Intracranial aneurysm, arteriovenous malformation;
12. Life expectancy of any advanced disease < 6 months;
13. Participating in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirofiban; Patients are treated with intravenous tenecteplase first, and patients who meet the selection criteria will be randomly assigned to either the tirofiban or placebo group in a 1:1 ratio. Patients assigned to the tirofiban group will be treated with intravenous tirofiban. It is recommended to start treatment as soon as possible (within 10 minutes recommended) after randomization. Tirofiban will be administered at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h. Aspirin placebo (1 tablet) and/or clopidogrel placebo (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.	Drug: Tirofiban Hydrochloride; Patients will receive a continuous intravenous infusion of tirofiban at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h after start of tenecteplase treatment within 4-24 hours. Aspirin placebo (1 tablet) and/or clopidogrel placebo (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.
Placebo Comparator: Placebo; All patients are treated with intravenous tenecteplase first, and patients who meet the selection criteria will be randomly assigned to either the tirofiban or placebo group in a 1:1 ratio. Patients assigned to the placebo group will be treated with intravenous saline. It is recommended to start treatment as soon as possible (within 10 minutes recommended) after randomization. Placebo will be administered at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h. Aspirin (1 tablet) and/or clopidogrel (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.	Drug: Placebo; Patients will receive a continuous intravenous infusion of placebo at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h after start of tenecteplase treatment within 4-24 hours. Aspirin (1 tablet) and/or clopidogrel (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent functional outcome	modified Rankin scale score of 0 to 1. modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death.	90 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal degree of disability	Ordinal degree of disability on the modified Rankin scale score at 90 days (shift analysis)	90 days post-randomization
Functionally independent	modified Rankin scale score of 0 to 2	90 days post-randomization
Ambulatory or bodily needs capable or better	modified Rankin scale score of 0 to 3	90 days post-randomization
Early neurologic improvement	defined as the National Institutes of Health Stroke Scale score at 48 hours after randomization, is reduced by 30% or more compared to the National Institutes of Health Stroke Scale score at randomization	48 hours post-randomization
Health-related quality of life	assessed with the European Quality Five Dimensions Five Level scale	90 days post-randomization
Symptomatic intracranial hemorrhage	defined as per the Heidelberg bleeding classification	48 hours post-randomization
Radiologic intracranial hemorrhage rate	diagnosed with intracranial hemorrhage (including bleeding in brain parenchyma, subarachnoid space, etc.) via radiologic examinations (e.g., computed tomography or magnetic resonance imaging	48 hours post-randomization
Mortality	The proportion of participants who die from any cause within 90 days after randomization in the study	90 days post-randomization
Incidence of non-hemorrhagic serious adverse events	such as pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc	Within 90 days post-randomization
Other serious adverse events	Serious adverse events that are not categorized as non-hemorrhagic (as listed in Outcome 10), including any unlisted severe medical events requiring medical intervention or leading to significant clinical deterioration	Within 90 days post-randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal degree of disability	Ordinal degree of disability on the modified Rankin scale score at 1 year (shift analysis)	1 year post-randomization
Excellent functional status	modified Rankin scale score 0 to 1 at 1 year	1 year post-randomization
Functionally independent	modified Rankin scale score 0 to 2 at 1 year	1 year post-randomization
Ambulatory or bodily needs capable or better	modified Rankin scale score 0 to 3 at 1 year	1 year post-randomization

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangxi Medical University
• Collaborators: Ganzhou People's Hospital
• Investigators: Principal Investigator: Zhongming Qiu, MD, Sun Yet-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: randomized trial; tenecteplase; tirofiban; intravenous thrombolysis
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Tyrosine; Tirofiban
• Other Study ID Numbers: SecondAHGuangxiMU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol, Statistical Analysis Plan, and Analytic Code will be shared after approval of a proposal from principal investigator 3 years after the trial results are revealed.
• IPD Sharing Time Frame: 3 years after the trial results are revealed.
• IPD Sharing Access Criteria: After approval of a proposal from principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No