A Multicenter, Three-Arm, Open-Label, Endpoint-Blinded Randomized Controlled Trial to Evaluate the Optimal Duration of Early Tirofiban After Intravenous Thrombolysis in Acute Ischemic Stroke

NCT07842185 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: INSTANT-2
• Study Type: interventional
• Target: 1,482
• Locations: 1 country
• Sites: 10

Brief Summary

Acute ischemic stroke is a leading cause of disability and mortality among dults in China. Although intravenous thrombolysis serves as first-line reperfusion therapy, nearly half of patients fail to achieve vascular recanalization. The reocclusion rate ranges from 14% to 34%, and many patients are left with residual neurological deficits. Early antiplatelet therapy initiated after thrombolysis may sustain persistent reperfusion and improve prognosis. However, current guidelines generally recommend delaying antiplatelet treatment until 24 hours post-thrombolysis due to bleeding risks, and direct evidence for the optimal initiation timing remains lacking. Tirofiban is a rapidly acting, short-half-life, reversible glycoprotein IIb/IIIa receptor antagonist. Previous studies indicate its potential benefits and acceptable safety when administered after intravenous thrombolysis. This is a multicenter, three-arm, open-label, endpoint-blinded randomized controlled trial. A total of 1482 non-cardioembolic patients without large or medium vessel occlusion and with residual neurological deficits (NIHSS ≥4) after thrombolysis will be enrolled. Participants will be randomly allocated to the tirofiban 24-hour group, tirofiban 48-hour group, or blank control group. The primary outcome is the proportion of patients with excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 90 days. Symptomatic intracranial hemorrhage and neurological outcomes will also be evaluated. The study aims to determine the optimal duration of tirofiban treatment after thrombolysis and provide high-level evidence for precise interventions in the acute phase of stroke.

Conditions

Acute Ischemic Stroke

Keywords

Intravenous Thrombolysis; acute ischemic stroke; tirofiban; alteplase; tenecteplase

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with mRS 0-1 at 90 days

  Percentage of participants achieving modified Rankin Scale (mRS) score 0 or 1 at 90 days after randomization.

  90 days after randomization

Secondary Outcomes (5)

• mRS score at 90 days

  90 days after randomization

• EQ-5D-5L score at 90 days

  90 days after randomization

• Proportion of patients with mRS 0-2 at 90 days

  90 days after randomization

• Proportion of patients with mRS 0-3 at 90 days

  90 days after randomization

• Proportion of early neurological improvement

  48 hours after randomization

Other Outcomes (3)

• Incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours

  Within 48 hours after randomization

• Incidence of any intracranial hemorrhage (any ICH) within 48 hours

  Within 48 hours after randomization

• 90-day mortality

  90 days after randomization

Study Arms (3)

Arm A: Tirofiban 24-hour group

EXPERIMENTAL

Arm A: Patients receive tirofiban for 24 hours after intravenous thrombolysis.

Drug: Tirofiban Injection

Arm B: Tirofiban 48-hour group

EXPERIMENTAL

Arm B: Patients receive tirofiban for 48 hours after intravenous thrombolysis.

Drug: Tirofiban Injection

Arm C: Standard care control group

ACTIVE COMPARATOR

No tirofiban is administered after intravenous thrombolysis.

Other: No Interventions

Interventions

Tirofiban Injection DRUG

Intravenous infusion of tirofiban will be initiated after intravenous thrombolysis and continued for 24 hours. The dosage regimen follows the trial protocol.

Arm A: Tirofiban 24-hour group

No Interventions OTHER

No tirofiban will be administered after intravenous thrombolysis. Patients receive routine standard clinical management according to hospital guidelines.

Arm C: Standard care control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Diagnosis of acute ischemic stroke meeting the diagnostic criteria from Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023, and the patient has received intravenous thrombolysis with tenecteplase, alteplase or reteplase.
• Disabling stroke remains at 2-24 hours after completion of intravenous thrombolysis. Disabling stroke is defined as NIHSS score ≥ 4, or single limb motor subscore ≥ 2.
• Written informed consent is obtained from the patient or legal representative.

You may not qualify if:

• Intracranial hemorrhage confirmed by CT or MRI after intravenous thrombolysis and prior to randomization.
• CTA/MRA/DSA demonstrates occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery, anterior cerebral artery, or vertebrobasilar artery.
• History of atrial fibrillation or suspected cardioembolic stroke. Platelet count \<100×10⁹/L on routine blood test.
• Renal insufficiency with estimated glomerular filtration rate (eGFR) \<30 mL/min.
• Pregnant or breastfeeding women.
• Pre-existing neurological or psychiatric disorders that interfere with neurological function assessment.
• History of bleeding disorders, severe cardiac, hepatic or renal disease, or sepsis.
• Brain tumor with mass effect on imaging (excluding small meningioma). Intracranial aneurysm or arteriovenous malformation (AVM).
• Advanced illness with life expectancy less than 6 months.
• Current participation in another clinical trial.
• Other conditions deemed unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• The Affiliated Ganzhou Hospital of Nanchang University: collaborator
• Xinqiao Hospital of Chongqing: lead

Study Sites (10)

Taihe County People's Hospital

Fuyang, Anhui, 236600, China

Location

Longyan First Hospital of Fujian Medical University

Longyan, Fujian, 364000, China

Location

Xiangtan Central Hospital (The Affiliated Hospital of Hunan University)

Xiangtan, Hunan, 411100, China

Location

Ganzhou People's Hospital

Ganzhou, Jiangxi, 341000, China

Location

Xingguo People's Hospital, Xinguo Hospital of Gannan Medical University

Ganzhou, Jiangxi, 342414, China

Location

Jingdezhen First People's Hospital

Jingdezhen, Jiangxi, 333000, China

Location

The First People's Hospital of Jingdezhen City

Jingdezhen, Jiangxi, 341000, China

Location

Jiujiang First People's Hospital

Jiujiang, Jiangxi, China

Location

Dalian Central Hospital

Dalian, Liaoning, 116000, China

Location

The First People's Hospital of Mianyang (Mianyang 404 Hospital)

Mianyang, Sichuan, 621000, China

Location

Related Publications (1)

• INSTANT Trial Authors for the INSTANT Investigators; Liu X, Zhang F, Zhang C, Li Z, Yuan G, Kong D, Xie S, Zhou M, Ye J, Lai Z, Li D, Xu H, Chen L, Cheng F, Shi Y, Chen B, Hu W, Liu H, Yin Y, Deng X, Xie Z, Li C, Shi J, Mei D, Liu B, Wang B, Zhou R, Liu J, Shen L, Hu H, Xiao G, Guan X, Yuan S, Lv X, Liang S, Zeng X, Chen Y, Cao W, Zheng C, Liu Y, Li J, Guan B, Lai T, Sun W, Zeng H, Zhang J, Li S, Sang H, Tang Y, Wang D, Lu M, Kaesmacher J, Yogendrakumar V, Pan S, Nogueira RG, Hong D, Goyal M, Thomalla G, Nguyen TN, Saver JL, Yang Q, Qiu Z, Zeng G. Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke: The INSTANT Randomized Clinical Trial. JAMA. 2026 Jun 9;335(22):1949-1958. doi: 10.1001/jama.2026.5245.

  PMID: 42100960 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tirofiban

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• zhongming qiu

  Xinqiao Hospital of the Army Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guoyong Zeng, doctor

CONTACT

+8613507079530; hsyygy@126.com

Fan Zhang, doctor

CONTACT

+8618970148470; zhappy0066@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants and treating investigators are unblinded (open-label). Outcome assessors for primary endpoint are blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 20, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): November 19, 2026
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): May 8, 2031
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Available starting 6 months after publication of the primary manuscript.
• Access Criteria: Interested researchers may submit a formal research proposal and data access request to the corresponding author. The study steering committee will review each application.

Locations

CN (10)