Intravenous Thrombolysis Combined With Tirofiban in Acute Ischemic Stroke

NCT07290751 | Recruiting Phase 4 DMC

• 1 other identifier: 2025-013
• Study Type: interventional
• Target: 976
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, prospective, double-blind, placebo-controlled, randomized trial (ANGEL-DRUG2) aims to evaluate the efficacy and safety of intravenous tirofiban following intravenous thrombolysis in patients with acute ischemic stroke who show insufficient neurological improvement after initial treatment. Eligible patients (≥18 years, baseline NIHSS ≥4, within 4.5 hours from last known well) will be randomized 1:1 to receive either tirofiban or placebo infusion for 24 hours, followed by standard oral antiplatelet therapy. The primary endpoint is the proportion of patients achieving functional independence (mRS 0-2) at 90 days. Secondary outcomes include changes in NIHSS score, vessel recanalization, infarct volume, distribution of mRS scores, recurrent stroke, and health-related quality of life. Safety outcomes focus on symptomatic intracranial hemorrhage and all-cause mortality. Approximately 976 patients will be enrolled across 30 sites in China.

Conditions

Acute Ischemic Stroke

Keywords

stroke; tirofiban; thrombolysis

Outcome Measures

Primary Outcomes (2)

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

  Proportion of patients with Modified Rankin Scale (mRS) 0-2, Modified Rankin Scale（0-6）, A lower MRS score indicates better functional status for the patient.

  90±7 days post-randomization

• Symptomatic Intracranial Hemorrhage (sICH) within 48 hours

  Heidelberg Bleeding Classification with clinical worsening criteria.

  Randomization to 48 hours

Secondary Outcomes (10)

• Change in NIHSS from baseline to 36±12 hours

  36±12 hours post-randomization

• Vascular recanalization rate assessed by CT/MR angiography

  36±12 hours post-randomization

• Change in infarct volume at 7±3 days/discharge

  7±3 days post-randomization or discharge

• mRS distribution

  7±3 days/discharge；90±7 days post-randomization

• Proportion with mRS 0-1 at 90 days

  90±7 days

Study Arms (2)

Arm A - Tirofiban

EXPERIMENTAL

Drug: Tirofiban

Arm B - Placebo

PLACEBO COMPARATOR

Other: Placebo (0.9% normal saline)

Interventions

Placebo (0.9% normal saline) OTHER

Matched normal saline infusion using the same dosing schedule and pump rates as the tirofiban arm (0.4 μg/kg/min for 30 minutes, then 0.1 μg/kg/min for 23.5 hours; total 24 hours). At the 20th hour of infusion, oral antiplatelet therapy (aspirin 100 mg once daily and/or clopidogrel 75 mg once daily) is initiated, overlapping with placebo infusion for 4 hours (bridge therapy). At 24 hours, placebo infusion is completed, and patients continue oral antiplatelet therapy per protocol.

Arm B - Placebo

Tirofiban DRUG

After intravenous thrombolysis, if neurological improvement is insufficient (NIHSS score decrease \<2 within 1 hour or NIHSS increase ≥1), tirofiban infusion is initiated within 1 hour. The regimen consists of 0.4 μg/kg/min for 30 minutes, followed by 0.1 μg/kg/min for 23.5 hours (total 24 hours). At the 20th hour of infusion, oral antiplatelet therapy (aspirin 100 mg once daily and/or clopidogrel 75 mg once daily) is initiated, overlapping with tirofiban for 4 hours (bridge therapy). At 24 hours, tirofiban infusion is completed, and patients continue oral antiplatelet therapy per protocol.

Arm A - Tirofiban

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.
• Pre-stroke modified Rankin Scale (mRS) score of 0-1.
• Acute ischemic stroke symptoms within 4.5 hours of last known well time.
• Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥4.
• Poor neurological improvement 1 hour after intravenous thrombolysis, defined as NIHSS decrease \<2 points, or neurological worsening within 1 hour, defined as NIHSS increase ≥1 point.
• Not planned for or not eligible for endovascular treatment.
• Subject or legally authorized representative can provide written informed consent.

You may not qualify if:

• Evidence of intracranial hemorrhage on imaging before randomization.
• Non-ischemic intracranial pathologies, such as vascular malformation, aneurysm, tumor, abscess, or demyelinating disease.
• Large or medium vessel stenosis requiring thrombectomy or intra-arterial thrombolysis.
• Contraindications to tirofiban, including but not limited to:Known hypersensitivity to tirofiban; Severe hepatic dysfunction (ALT \>2× ULN or AST \>2× ULN); Severe renal dysfunction (serum creatinine \>1.5× ULN); Advanced heart failure (NYHA class III-IV); Coagulation disorders or history of systemic bleeding; History of thrombocytopenia or neutropenia; Prior drug-induced hematologic disease or liver dysfunction; Leukopenia (\<2×10\^9/L) or platelet count \<100×10\^9/L.
• Use of tirofiban or other GP IIb/IIIa inhibitors before randomization, or planned use of such agents after randomization.
• Definite cardioembolic source, including but not limited to: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical prosthetic heart valves, infective endocarditis, history of intracardiac thrombus, myocardial infarction within 3 months, dilated cardiomyopathy, spontaneous left atrial echo contrast, or left ventricular ejection fraction \<30%.
• Pregnancy or lactation.
• Expected survival \<6 months.
• Pre-existing neurological or psychiatric disorders that may interfere with outcome assessment.
• Unlikely to complete 90-day follow-up.

Sponsors & Collaborators

• Beijing Anzhen Hospital: lead

Study Sites (1)

Beijing Anzhen Hospital,Capital Medical University

Beijing, Beijing Municipality, 101118, China

RECRUITING

Related Publications (12)

• Hilkens NA, Casolla B, Leung TW, de Leeuw FE. Stroke. Lancet. 2024 Jun 29;403(10446):2820-2836. doi: 10.1016/S0140-6736(24)00642-1. Epub 2024 May 14.

  PMID: 38759664 BACKGROUND

• Powers WJ, Rabinstein AA, Ackerson T, et al (2019) Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for HealthcareProfessionals From the American Heart Association/American Stroke Association. Stroke. https://doi.org/10.1161/STR.0000000000000211

  BACKGROUND

• Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, de la Ossa NP, Strbian D, Tsivgoulis G, Turc G. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021 Mar;6(1):I-LXII. doi: 10.1177/2396987321989865. Epub 2021 Feb 19.

  PMID: 33817340 BACKGROUND

• Wang C, Yi X, Zhang B, Liao D, Lin J, Chi L. Clopidogrel plus aspirin prevents early neurologic deterioration and improves 6-month outcome in patients with acute large artery atherosclerosis stroke. Clin Appl Thromb Hemost. 2015 Jul;21(5):453-61. doi: 10.1177/1076029614551823. Epub 2014 Sep 23.

  PMID: 25248816 BACKGROUND

• Guo ZN, Zhang KJ, Zhang P, Qu Y, Abuduxukuer R, Nguyen TN, Chen HS, Yang Y. Early tirofiban administration after intravenous thrombolysis in acute ischemic stroke (ADVENT): Study protocol of a multicenter, randomized, double-blind, placebo-controlled clinical trial. Eur Stroke J. 2024 Jun;9(2):510-514. doi: 10.1177/23969873231225069. Epub 2024 Jan 9.

  PMID: 38196129 BACKGROUND

• Liu R, Liang Z, Li W, Zhan Y, Xu L, Yang S, Zheng G, Jiang L, Xie L, Sun Z, Hu Y. Adding Tirofiban on Top of Recombinant Tissue Plasminogen Activator May Improve Clinical Outcome in Acute Stroke Patients. J Stroke. 2024 Jan;26(1):121-124. doi: 10.5853/jos.2023.02250. Epub 2024 Jan 30. No abstract available.

  PMID: 38326710 BACKGROUND

• Liang Z, Zhang J, Huang S, Yang S, Xu L, Xiang W, Zhang M. Safety and efficacy of low-dose rt-PA with tirofiban to treat acute non-cardiogenic stroke: a single-center randomized controlled study. BMC Neurol. 2022 Jul 27;22(1):280. doi: 10.1186/s12883-022-02808-w.

  PMID: 35897006 BACKGROUND

• Yang M, Huo X, Miao Z, Wang Y. Platelet Glycoprotein IIb/IIIa Receptor Inhibitor Tirofiban in Acute Ischemic Stroke. Drugs. 2019 Apr;79(5):515-529. doi: 10.1007/s40265-019-01078-0.

  PMID: 30838514 BACKGROUND

• Jiao Y, Wang X, Guan Y, Wang X, Li Z, Xiang X, Zhang Z. Therapeutic Efficacy of Tirofiban Combined With Thrombus Aspiration and Stent Thrombectomy in the Treatment of Large Vessel Occlusion Ischemic Stroke. Neurologist. 2025 May 1;30(3):140-144. doi: 10.1097/NRL.0000000000000603.

  PMID: 39648705 BACKGROUND

• Zhang Y, Zhang QQ, Fu C, Wang L, Zhang GQ, Cao PW, Chen GF, Fu XM. Clinical efficacy of tirofiban combined with a Solitaire stent in treating acute ischemic stroke. Braz J Med Biol Res. 2019;52(10):e8396. doi: 10.1590/1414-431X20198396. Epub 2019 Sep 16.

  PMID: 31531525 BACKGROUND

• Higgins JPT, Thomas J, Chandler J, et al (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Available from www.training.cochrane.org/handbook.

  BACKGROUND

• de Almeida Monteiro G, Leite M, Goncalves OR, Ferreira MY, Mutarelli A, Marinheiro G, Araujo B, Leal PRL, Ribeiro EML, Figueiredo EG, Telles JPM. Efficacy and safety of intravenous tirofiban combined with reperfusion therapy versus reperfusion therapy alone in acute ischemic stroke: a meta-analysis of randomized controlled trials. J Thromb Thrombolysis. 2025 Apr;58(4):526-537. doi: 10.1007/s11239-025-03094-2. Epub 2025 Apr 1.

  PMID: 40167884 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tirofiban; Saline Solution

Condition Hierarchy (Ancestors)

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Xiaochuan Huo

CONTACT

+8613716292262; huoxiaochuan@126.com

Xin Tong

CONTACT

+8617810651085; Tomice123@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: December 18, 2025
• Study Start: November 11, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)