Study on Tirofiban With Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction

NCT05310968 | Completed Phase 4 DMC

• 1 other identifier: KY2021-089-08
• Study Type: interventional
• Target: 970
• Locations: 1 country
• Sites: 37

Brief Summary

Perforating artery territorial infarction (PAI) refers to a single ischemic lesion in a single perforating arterial territory and branch atheromatous disease (BAD) is an important type. BAD related stroke accounts for 10%-15% ischemic cerebral infarction and is closely related to early neurological deterioration (END). Among patients with single ischemic lesion in other study, dual antiplatelet (clopidogrel plus aspirin) did not significantly reduce the risk of recurrent stroke. The primary purpose of this study is to assess the efficacy and safety of tirofiban combined with aspirin versus placebo combined with aspirin in reducing the risk of stroke and END in patients with BAD.

Conditions

Branch Atheromatous Disease

Keywords

branch atheromatous disease; perforating artery territorial infarction; tirofiban; aspirin; randomized controlled trial; multicenter study; double blind study; placebo-controlled

Outcome Measures

Primary Outcomes (1)

• new stroke or END(early neurological deterioration）

  1. Symptoms and signs of acute neurological deficits caused by sudden focal or whole brain, spinal cord, or retinal vascular damage, which are related to cerebral circulatory disorders, including hemorrhagic and ischemic stroke. 2. NIHSS score increasing by ≥ 2 points, or the score increasing by≥1 in either the motor or consciousness level within 7 days after randomization and intracranial hemorrhage is excepted by CT or MRI. Exacerbations not attributable to stroke are also excluded such as cardiac failure, liver and renal failure, etc.

  90 days after randomization

Secondary Outcomes (5)

• new stroke or END

  24 hours and 7 days after randomization

• Composite vascular events

  90 days after randomization

• Disability or death

  90 days after randomization

• Improvement of neurological function

  24 hours, 7 days, and 90 days after randomization

• EQ-5D-5L Scale

  90 days after randomization

Other Outcomes (5)

• Moderate or severe bleeding events

  90 days after randomization

• Symptomatic and non-symptomatic intracranial hemorrhage

  90 days after randomization

• Vascular death

  90 days after randomization

Study Arms (2)

Tirofiban group

EXPERIMENTAL

This group will receive tirofiban and aspirin. Day 1: Tirofiban injected intravenously for 24 hours and aspirin of 100-300 mg. Tirofiban will be injected at 0.4 ug/kg/ min for the first 30 minutes and 0.1 ug/kg/min for the next 24 hours. Day 2-90: Aspirin 100mg per day.

Drug: Tirofiban hydrochloride sodium chloride injection; Drug: Aspirin

Tirofiban placebo group

PLACEBO COMPARATOR

This group will receive tirofiban placebo and aspirin. Day 1: Tirofiban placebo injected intravenously for 24 hours and aspirin of 100-300 mg. The placebo will be injected at the same rate with Tirofiban group. Day 2-90: Aspirin 100mg per day.

Drug: Tirofiban hydrochloride sodium chloride injection placebo; Drug: Aspirin

Interventions

Aspirin DRUG

Day 1: Aspirin 100-300mg per day Day 2-90: Aspirin 100mg per day

Tirofiban group; Tirofiban placebo group

Tirofiban hydrochloride sodium chloride injection DRUG

Day 1: Tirofiban will be given by bolus injection at 0.4ug/kg/min for the first 30 minutes, followed by a continuous infusion at 0.1ug/kg/min for the next 24 hours.

Tirofiban group

Tirofiban hydrochloride sodium chloride injection placebo DRUG

Day 1: Tirofiban placebo will be injected at the same rate with experimental group.

Tirofiban placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old;
• Male or female;
• Within 48 hours of onset;
• Clinical symptoms and signs suggest acute single infarction of penetrating artery territory (no cortical involvement, no multifocal involvement, NIHSS ≤10 and consciousness-1a ≤1);
• DWI suggests single infarction (diameter \< 30mm) of penetrating artery territory which involves at least 2 axial layers, or its maximum diameter ≥15mm, or it is connected to the ventral surface of the pons, closing to but not crossing the midline, and located in one side;
• No severe stenosis (defined as \<70%) of parent artery;
• The patient or his / her legal representative is able and willing to sign the informed consent.

You may not qualify if:

• History of intracranial hemorrhage
• History of intracranial tumors, cerebral arteriovenous malformation, or aneurysm;
• Emergency endovascular intervention or intravenous thrombolysis before randomization;
• Dual antiplatelet therapy currently or within 14 days of randomization (excluding use of aspirin and clopidogrel after onset without loading dose of clopidogrel);
• Use of other antiplatelet drugs (ticagrelor, cilostazol, etc.), anticoagulant drugs, snake venom, defibrase, lumbrukinase or other defibrase treatments after onset;
• Expected long-term use of non-investigational antiplatelet drugs or non-steroidal anti-inflammatory drugs;
• With severe stenosis (\> 70%) of parent artery giving off responsible penetrating artery;
• Definite indications for anticoagulation (suspicion of cardioembolism, e.g. atrial fibrillation, known heart valve prosthesis, atrial myxoma, endocarditis, etc.) or indications for dual antiplatelet therapy (e.g. recent coronary or cerebral artery stent implantation);
• Severe hepatic or renal insufficiency before randomization (severe hepatic insufficiency refers to ALT or AST \> 3 times the upper limit of normal; severe renal insufficiency refers to creatinine clearance rate (CCr) \< 30ml/min);
• Hemorrhagic tendency (including but not limited to)：PLT\<100×10\^9/L; heparin treatment within 48h; APTT ≥ 35s; current use of warfarin, INR \> 1.7; current use of novel oral anticoagulants; current use of direct thrombin or factor Xa inhibitor;
• Resistant hypertension which could not be controlled by medicine (SBP \> 180mmHg or DBP \> 110mmHg);
• History of obvious head trauma within three months of randomization;
• History of intracranial or intramedullary surgery within three months of randomization;
• History of major surgery or severe physical trauma within one month of randomization;
• Severe neurological defects (mRS ≥ 2) before the onset;

Sponsors & Collaborators

• GrandPharma (China) Co., Ltd.: collaborator
• Beijing Tiantan Hospital: lead

Study Sites (37)

The First Hospital of Fangshan District Beijing

Beijing, Beijing Municipality, China

Location

School of Medicine, Xiamen University

Zhangzhou, Fujian, China

Location

Guizhou Provincial People's Hospital

Guiyang, Guizhou, China

Location

Hejian People's Hospital

Hejian, Hebei, China

Location

Tangshan Gongren Hospital

Tangshan, Hebei, China

Location

The People's Hospital of Qinghe County

Xingtai, Hebei, China

Location

Mengzhou People's Hospital

Henan, Henan, China

Location

Xiuwu People's Hospital

Jiaozuo, Henan, China

Location

Jiyuan Hospital of Traditional Chinese Medicine

Jiyuan, Henan, China

Location

The Second Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

Location

Tanghe County People's Hospital

Nanyang, Henan, China

Location

The First People's Hospital of Nanyang

Nanyang, Henan, China

Location

Suixian Hospital of Traditional Chinese Medicine

Shangqiu, Henan, China

Location

The People's Hospital of Biyang County

Zhumadian, Henan, China

Location

Shaodong People's Hospital

Shaoyang, Hunan, China

Location

Baotou Central Hospital

Baotou, Inner Mongolia, China

Location

The First Affiliate Hospital of Baotou Medical College

Baotou, Inner Mongolia, China

Location

Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong)

Nantong, Jiangsu, China

Location

The People's Hospital of Suxitong Science & Technology Inductrial Park

Nantong, Jiangsu, China

Location

The Affiliated Shuyang Hospital of Xuzhou Medical University

Suqian, Jiangsu, China

Location

China-Japan Union Hospital of Jilin University

Changchun, Jilin, China

Location

Benxi Central Hospital

Benxi, Liaoning, China

Location

The First People's Hospital of Xianyang

Xianyang, Shaanxi, China

Location

Ningjin People's Hospital

Dezhou, Shandong, China

Location

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Jinan, Shandong, China

Location

Guanxian People's Hospital

Liaocheng, Shandong, China

Location

Liaocheng Central Hospital

Liaocheng, Shandong, China

Location

The People's Hospital of Gaotang County

Liaocheng, Shandong, China

Location

The Second People's Hospital of Liaocheng

Liaocheng, Shandong, China

Location

The Third People's Hospital of Liaocheng

Liaocheng, Shandong, China

Location

The People's Hospital of Linqing

Linqing, Shandong, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Weihai Wendeng District People's Hospital

Weihai, Shandong, China

Location

Zibo Municipal Hospital

Zibo, Shandong, China

Location

Changzhi People's Hospital

Changzhi, Shanxi, China

Location

Jincheng People's Hospital

Jincheng, Shanxi, China

Location

Wanrong County People's Hospital

Yuncheng, Shanxi, China

Location

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• Berberich A, Schneider C, Reiff T, Gumbinger C, Ringleb PA. Dual Antiplatelet Therapy Improves Functional Outcome in Patients With Progressive Lacunar Strokes. Stroke. 2019 Apr;50(4):1007-1009. doi: 10.1161/STROKEAHA.118.023789.

  PMID: 30841818 BACKGROUND

• Coull AJ, Lovett JK, Rothwell PM; Oxford Vascular Study. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ. 2004 Feb 7;328(7435):326. doi: 10.1136/bmj.37991.635266.44. Epub 2004 Jan 26.

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• Jeong HG, Kim BJ, Yang MH, Han MK, Bae HJ. Neuroimaging markers for early neurologic deterioration in single small subcortical infarction. Stroke. 2015 Mar;46(3):687-91. doi: 10.1161/STROKEAHA.114.007466. Epub 2015 Feb 12.

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• Cohen JE, Rabinstein A, Gomori JM, Leker RR. Capsular warning syndrome and crescendo lacunar strokes after atherosclerotic stenosis of the recurrent artery of Heubner. J Clin Neurosci. 2012 Dec;19(12):1730-3. doi: 10.1016/j.jocn.2012.04.010. Epub 2012 Sep 19.

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• Liao X, Feng S, Wang Y, Pan Y, Chen W, Qu H, Zhao X, Liu L, Wang Y, Wang Y. Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial. Stroke Vasc Neurol. 2024 Feb 27;9(1):75-81. doi: 10.1136/svn-2022-002284.

  PMID: 37220998 DERIVED

MeSH Terms

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Yilong Wang, PhD，MD

  Beijing Tiantan Hospital, Capital Medical University, Beijing, China

  PRINCIPAL INVESTIGATOR

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: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: March 27, 2022
• First Posted: April 5, 2022
• Study Start: November 12, 2022
• Primary Completion: February 17, 2025
• Study Completion: September 1, 2025
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (37)