Tirofiban for the Prevention of Neurological Deterioration in Acute Ischemic Stroke (TREND)

Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration of Patients With Acute Ischemic Stroke: A Randomized Controlled Trial

Currently, dual antiplatelet therapy with aspirin and clopidogrel (with loading doses) is widely used for patients with acute ischemic stroke. However, immediate, potent and reversible inhibition of platelet aggregation is not possible. Additionally, more than 5% patients have aspirin resistance and more than 15% patients have clopidogrel resistance. Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (Tirofiban) receptor blocker with fast onset and offset of actions will provide more desired antiplatelet effects in the setting of acute ischemic stroke, especially in patients with high risk of neurological deterioration. This study will measure the anti-platelet effects of Tirofiban in patients with acute ischemic stroke who had high risk of neurological deterioration.

Study Overview

• Status: Recruiting
• Conditions: Acute Stroke
• Intervention / Treatment: Drug: Tirofiban Hydrochloride; Drug: Oral antiplatelet

• Study Type: Interventional
• Enrollment (Anticipated): 420
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Qingfeng Ma, M.D.; Phone Number: 010-83199430; Email: m.qingfeng@163.com
• Study Contact Backup: Name: Wenbo Zhao, M.D.; Phone Number: 86-13120136877; Email: zhaowb.cool@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Qingfeng Ma, M.D.
      • Contact: Wenbo Zhao, M.D.
      • Principal Investigator: Qingfeng Ma
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Luhe Hospital, Capital Medical University
      • Contact: Huishan Du, M.D.
      • Contact: Xiaokun Geng, M.D.
  • Henan
    • Luoyang, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Junqiang Yan, M.D.
    • Nanyang, Henan, China
      • Recruiting
      • Nanyang Central Hospital
      • Contact: Changming Wen, M.D.
    • Nanyang, Henan, China
      • Recruiting
      • Nanyang Second General Hospital
      • Contact: Jinhui Qin, M.D.
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Provincial People's Hospital
      • Contact: Ziliang Wang, M.D.
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • First Affiliated Hospital of Zhengzhou University
      • Contact: Yuming Xu
  • Hubei
    • Wuhan, Hubei, China
      • Active, not recruiting
      • The Third People's Hospital of Hubei Province
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Hunan Provincial People's Hospital
      • Contact: Xiaoping Gao, M.D.
  • Inner Mongolia Autonomous Region
    • Baotou, Inner Mongolia Autonomous Region, China
      • Recruiting
      • Sinapharm North Hospital
      • Contact: Lifei Xing, M.D.
    • Ordos, Inner Mongolia Autonomous Region, China
      • Recruiting
      • Ordos Central Hospital
      • Contact: Xiaojun Hao
    • Tongliao, Inner Mongolia Autonomous Region, China
      • Recruiting
      • Tongliao City Hosptial
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • NanJing Drum Tower Hospital
      • Contact: Yu Xu, M.D.
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Active, not recruiting
      • Jiangxi Provincial People's Hospital
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Shandong Provincial Hospital
      • Contact: Qinjian Sun, M.D.
    • Jinan, Shandong, China
      • Active, not recruiting
      • ShanDong Provincial QianFoShan Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • West China Hospital of Sichuan University
      • Contact: Bo Wu, M.D.
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Beichen Hospital of Traditional Chinese Medicine
      • Contact: Ruixian Wang, M.D.
    • Tianjin, Tianjin, China
      • Active, not recruiting
      • TEDA Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute ischemic stroke with 24 hours of symptom onset.
2. NIHSS≥4 and ≤20 points, and the paralyzed limbs is able to actively move the muscle (standardized motor examination rating scale of 2 or much higher).
3. Age 18-80 years old.
4. Informed consent obtained from patient or acceptable patient's surrogate.

Exclusion Criteria:

1. Treated with intravenous or endovascular thrombectomy for the indexed acute ischemic stroke.
2. Acute ischemic stroke caused by determined or suspected cardioembolism.
3. Acute ischemic stroke caused by other determined caused, including moyamoya disease, artery dissection, arteritis, and etc.
4. Pre-stroke mRS ≥2 or the paralyzed limbs are dyskinesia before stroke.
5. Known hematochezia, gastrointestinal bleeding and any other bleeding.
6. Allergy to tirofiban or its solvents.
7. Patients suffered from severe diseases, including malignant tumor, liver cirrhosis, kidney failure, congestive heart failure, and etc.
8. Gastrointestinal or genitourinary tract bleeding within 1 years.
9. Determined coagulation disorders, platelet dysfunction, or platelet count <100*109/L.
10. Major surgical operation or severe trauma within 1 month.
11. Hemorrhagic retinopathy.
12. Chronic hemodialysis.
13. Uncontrolled hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg.
14. Acute pericarditis.
15. Other conditions that determined by the investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirofiban+Oral antiplatelet therapy; Patients will receive Tirofiban in the first 72 hours and bridge to oral antiplatelet therapy thereafter.	Drug: Tirofiban Hydrochloride; Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion for 71.5 hours.; Drug: Oral antiplatelet; Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.
Active Comparator: Oral antiplatelet therapy; Patients will receive oral antiplatelet therapy alone.	Drug: Oral antiplatelet; Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a change in NIHSS by ≥ 4 points compared to enrollment NIHSS.	National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.	Within 72 hours of intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the NIHSS	National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.	0-30 days of intervention.
Change of the Scandinavian Stroke Scale	Scandinavian Stroke Scale (SSS): stroke symptom severity scale with a range of 0-58. Lower score means more severe stroke symptoms.	0-30 days of intervention.
The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS).	The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).	0-90 days.
Rate of symptomatic intracerebral hemorrhage.		0-90 days
Number of Participants experienced adverse events		0-90 days.

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• 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.
• Zhao W, Che R, Shang S, Wu C, Li C, Wu L, Chen J, Duan J, Song H, Zhang H, Ling F, Wang Y, Liebeskind D, Feng W, Ji X. Low-Dose Tirofiban Improves Functional Outcome in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy. Stroke. 2017 Dec;48(12):3289-3294. doi: 10.1161/STROKEAHA.117.019193. Epub 2017 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: July 25, 2020
• First Submitted That Met QC Criteria: July 25, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 16, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Neurological deterioration; Stroke progression
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Tirofiban
• Other Study ID Numbers: Trend

Drug and device information, study documents

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