Tirofiban for the Prevention of Early Neurological Deterioration After Intravenous Thrombolysis in Acute Ischemic Stroke

NCT06587347 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: TREND-2
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, multicenter, randomized, controlled, open-label, blinded endpoint trial to evaluate the safety and efficacy of intravenous administration of tirofiban for preventing early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke.

Conditions

Acute Stroke; Ischemic Stroke, Acute; Cerebral Infarction

Keywords

Acute ischemic stroke; Neurological deterioration; Stroke progression; intravenous thrombolysis; Antiplatelet therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients experiencing neurological deterioration within 24 hours after intravenous thrombolysis.

  National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale ranging from 0-42. A higher score means more severe stroke symptoms. Neurological deterioration is defined as an increase in NIHSS by ≥ 4 points compared to the lowest NIHSS.

  Within 24 hours after intravenous thombolysis.

Secondary Outcomes (17)

• Change of the NIHSS

  7 days or discharge after intravenous thrombolytic therapy

• The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 30-day follow up.

  30 days after stroke

• The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.

  90 days after stroke

• The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30-day follow up.

  30 days after stroke

• The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up.

  90 days after stroke

Other Outcomes (1)

• Biomarkers levels of groups

  Within 24 hours of intervention

Study Arms (2)

Tirofiban Group

EXPERIMENTAL

Patients will receive tirofiban in the first 24 hours after intravenous thrombolysis, then bridge to oral antiplatelet therapy.

Drug: Tirofiban Hydrochloride

Control group

ACTIVE COMPARATOR

Aspirin, clopidogrel, or other antiplatelet drugs will be used in principle after 24 hours of thrombolytic therapy or until the primary outcome occurs.

Drug: Standard medical treatment (SMT)

Interventions

Tirofiban Hydrochloride DRUG

Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion until 24 hours after Intravenous thrombolytic therapy, or use a loading dose, 25 μg/kg, administrated within 3 minutes, then 0.15μg/kg/min infusion until 24 hours after Intravenous thrombolytic therapy.

Tirofiban Group

Standard medical treatment (SMT) DRUG

Patients will receive standard antiplatelet therapy.

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 old;
• Acute ischemic stroke treated with intravenous thrombolysis with alteplase or tenecteplase within 4.5 hours of onset or time last known well and can receive the study drug treatment within 3 hours of initiating intravenous thrombolysis.
• Residual NIHSS score ≥ 5 points at randomization (at least 1 hour after intravenous thrombolytic therapy).
• Post-thrombolysis imaging shows that the offending artery is consistent with moderate or severe intracranial atherosclerotic stenosis (within 50%\~99%)
• Informed consent obtained from patients or their acceptable surrogates.

You may not qualify if:

• Intracranial hemorrhage confirmed by imaging post-thrombolysis.
• Stroke caused by other determined causes, including moyamoya disease, artery dissection, arteritis, etc.
• Scheduled for or received endovascular treatment after onset.
• Definite or suspected cardioembolic stroke.
• Definite anticipation of developing indications for anticoagulant therapy during the study period (e.g., atrial fibrillation, mechanical heart valve, deep vein thrombosis, pulmonary embolism, antiphospholipid syndrome, hypercoagulable state).
• Use of antiplatelet or anticoagulant therapy within one week pre-stroke.
• Pre-stroke mRS score ≥ 2.
• Severe consciousness disturbance with NIHSS item 1a (level of consciousness) \>1 point at randomization.
• History of tirofiban allergy or its solvents.
• History of platelet count \< 100 × 109/L caused by tirofiban.
• Major surgical operation within 6 weeks.
• Major systemic hemorrhage within 30 days;
• Determined coagulation disorders, platelet dysfunction, or platelet count \< 100\*109/L.
• Currently pregnant or lactating;
• Uncontrolled hypertension with systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg.

Sponsors & Collaborators

• Capital Medical University: lead

Study Sites (1)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

Related Publications (3)

• Zhao W, Li S, Li C, Wu C, Wang J, Xing L, Wan Y, Qin J, Xu Y, Wang R, Wen C, Wang A, Liu L, Wang J, Song H, Feng W, Ma Q, Ji X; TREND Investigators. Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2024 Jun 1;81(6):594-602. doi: 10.1001/jamaneurol.2024.0868.

  PMID: 38648030 BACKGROUND

• Zi W, Song J, Kong W, Huang J, Guo C, He W, Yu Y, Zhang B, Geng W, Tan X, Tian Y, Liu Z, Cao M, Cheng D, Li B, Huang W, Liu J, Wang P, Yu Z, Liang H, Yang S, Tang M, Liu W, Huang X, Liu S, Tang Y, Wu Y, Yao L, Shi Z, He P, Zhao H, Chen Z, Luo J, Wan Y, Shi Q, Wang M, Yang D, Chen X, Huang F, Mu J, Li H, Li Z, Zheng J, Xie S, Cai T, Peng Y, Xie W, Qiu Z, Liu C, Yue C, Li L, Tian Y, Yang D, Miao J, Yang J, Hu J, Nogueira RG, Wang D, Saver JL, Li F, Yang Q; RESCUE BT2 Investigators. Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion. N Engl J Med. 2023 Jun 1;388(22):2025-2036. doi: 10.1056/NEJMoa2214299.

  PMID: 37256974 BACKGROUND

• Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, Zhao W, Ren M, Wu D, Ding J, Song H, Wang Y, Ma Q, Ji X. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019 Dec;50(12):3481-3487. doi: 10.1161/STROKEAHA.119.026240. Epub 2019 Oct 1.

  PMID: 31570084 BACKGROUND

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Cerebral Infarction

Interventions

Tirofiban

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

XunMing Ji, MD, PD

CONTACT

86-10-8319-9439; jixm@ccmu.edu.cn

Wenbo Zhao, MD, PD

CONTACT

86-10-8319-9048; zhaowb@xwh.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 19, 2024
• Study Start: November 20, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 29, 2024

Record last verified: 2024-08

Locations

CN (1)