Efficacy and Safety of Tirofiban for Patients With BAD (BRANT)

NCT06037889 | Completed Phase 3 DMC

• 1 other identifier: BAD-RCT202201
• Study Type: interventional
• Target: 516
• Locations: 1 country
• Sites: 25

Brief Summary

Branch atheromatous disease (BAD)-related stroke, characterized by subcortical single infarcts without severe stenosis of the large artery, but with a clear atherosclerotic mechanism, is now regarded as a separate stroke type. BAD is associated with early neurological deterioration and poor prognosis, but is lack of effective therapy. The goal of this randomized controlled trial is to test the efficacy and safety of intravenous tirofiban in patients with acute ischemic stroke caused by branch atheromatous disease. The main question it aims to answer is: Compared with standard antiplatelet therapy based on current stroke guideline, whether tirofiban used in acute phase of BAD could improve the proportion of excellent functional outcome (modified Rankin Scale: 0-1) at 90 days. Researcher will also compare the rate of major bleeding between treatment and control groups.

Conditions

Branch Atheromatous Disease

Keywords

Branch atheromatous disease; Tirofiban; Stroke; Treatment Outcome; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Excellent functional outcome

  Primary efficacy outcome: Excellent functional outcome is defined as modified Rankin Scale score: 0-1. Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Death.

  90 days

Secondary Outcomes (27)

• Excellent functional outcome

  7 days

• mRS

  7 and 90 days

• Early neurological deterioration

  7 days of randomization

• NIHSS score

  7 days and 90 days

• Barthel index score

  90 days

Study Arms (2)

Tirofiban group

EXPERIMENTAL

Intravenous tirofiban will be administered immediately after randomization for a total duration of 48h with a loading dose of 0.4ug/kg/min\*30min, followed by a maintenance dose of 0.1ug/kg/min\*47.5h.

Drug: Tirofiban

Standard antiplatelet therapy group

ACTIVE COMPARATOR

Standard antiplatelet therapy based on Chinese stroke guideline will be administered after randomization for a total duration of 48h, as the two following types: 1) aspirin 150-300 mg qd, or 2) aspirin 100 mg qd plus clopidogrel 75 mg qd. The time for administration of antiplatelet drugs will be determined by the doctor in conjunction with the participants' use of antiplatelet or anticoagulant medication in the 24h prior to randomization, but the drug should be given as soon as possible after randomization.

Drug: Aspirin tablet; Drug: Clopidogrel tablet

Interventions

Tirofiban DRUG

Tirofiban, a GPIIb/IIIa receptor inhibitor. Intravenous administration.

Also known as: Tirofiban Hydrochloride and Sodium Chloride Injection

Tirofiban group

Aspirin tablet DRUG

Aspirin. Oral administration.

Standard antiplatelet therapy group

Clopidogrel tablet DRUG

Clopidogrel. Oral administration.

Standard antiplatelet therapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-75 years old
• Acute ischemic stroke
• Time from onset to randomization ≤48h; if onset time is unknown, time from last known well to randomization ≤48h
• Meet the following BAD Diagnostic Imaging Criteria
• DWI infarcts: single (isolated) deep (subcortical) infarcts;
• The culprit arteries are either Lenticulostriate artery (LSA) or Paramedian pontine artery (PPA), and the infarct lesion on DWI conforms to one of the following characteristics (A/B): A. LSA: 1) "Comma-like" infarct lesions with "Fan-shaped" extension from bottom to top in the coronal plane; or 2) ≥ 3 layers (layer thickness 5-7 mm) on axial DWI brain images; B. PPA: The infarct lesion extends from the deep pons to the ventral pons on the axial DWI brain images;
• No more than 50% stenosis on the parent artery of the criminal artery (i.e. corresponding basilar or middle cerebral artery) (Confirmed by magnetic resonance angiography \[MRA\] or computed tomography angiography \[CTA\] or digital substraction angiography \[DSA\]).
• Singed informed consent by the patient or legally authorized representatives.

You may not qualify if:

• Transient ischemic attack (TIA)
• Intracranial hemorrhagic diseases, vascular malformations, aneurysms, brain abscesses, malignant space-occupying lesions, or other non-ischemic intracranial lesions detected by baseline CT/MRI, or MRA/CTA/DSA;
• Presence of ≥50% stenosis in extracranial artery in tandem relationship ipsilateral to the lesion;
• Cardiogenic embolism: atrial fibrillation, myocardial infarction, heart valve disease, dilated cardiomyopathy, infective endocarditis, atrioventricular block disease, heart rate less than 50 beats per minute
• Have received or plan to receive endovascular therapy or thrombolysis after onset;
• Stroke of other clear causes, e.g., moyamoya disease, arterial dissection, vasculitis, etc.
• modified Rankin Scale ≥2 before onset
• Use of tirofiban within 1 week before or after onset
• Low platelets (\<100×10\^9 /L), or Prothrombin time \>1.3 times of the upper normal limit, or INR \>1.5, or other systemic hemorrhagic tendencies such as hematologic disorders
• Elevation of ALT or AST more than 1.5 times the upper normal limit;
• Glomerular filtration rate \<60 ml/min/1.73m\^2
• Known malignant tumors
• History of trauma or major surgical intervention within 6 weeks prior to onset
• History of intracranial hemorrhage
• Active or recent history(within 30 days prior to onset) of clinical bleeding (e.g., gastrointestinal bleeding)

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Pharmaron (Chengdu) Clinical Services Co., Ltd.: collaborator

Study Sites (25)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Beijing Shunyi Hospital

Beijing, Beijing Municipality, 101300, China

Location

Beijing Shijitan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

The First Hospital of Tsinghua University

Beijing, Beijing Municipality, China

Location

The second hospital of Baoding

Baoding, Hebei, 071051, China

Location

Botou City Hospital

Botou, Hebei, China

Location

Cangzhou Central Hospital

Cangzhou, Hebei, China

Location

Chengde Central Hospital

Chengde, Hebei, 067024, China

Location

Affiliated Hospital of Chifeng University

Chifeng, Hebei, 024099, China

Location

Hengshui People's Hospital

Hengshui, Hebei, 053099, China

Location

North China University of Science and Technology Affiliated Hospital

Tangshan, Hebei, 063000, China

Location

The Second Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Yellow River SANMENXIA Hospital

Sanmenxia, Henan, China

Location

The First People's Hospital of Shangqiu

Shangqiu, Henan, 476005, China

Location

The First Affiliated Hospital of Xinxiang Medical Unversity

Xinxiang, Henan, 453100, China

Location

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221009, China

Location

Meihekou Central Hospital

Meihekou, Jilin, 135022, China

Location

Shengli Oilfield Central Hospital

Dongying, Shandong, 257099, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Deyang People's Hospital

Deyang, Sichuan, 618099, China

Location

Mianyang Central Hospital

Mianyang, Sichuan, 621099, China

Location

The First People's Hospital of Yibin

Yibin, Sichuan, 644000, China

Location

The Second People's Hospital of Yibin

Yibin, Sichuan, 644000, China

Location

The Second Hospital of Tianjin Medical University

Tianjing, Tianjing, 300211, China

Location

Tibet Autonomous Region People's Hospital

Lhasa, Tibet, 850000, China

Location

Related Publications (26)

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• Park MG, Oh EH, Kim BK, Park KP. Intravenous tissue plasminogen activator in acute branch atheromatous disease: Does it prevent early neurological deterioration? J Clin Neurosci. 2016 Nov;33:194-197. doi: 10.1016/j.jocn.2016.04.011. Epub 2016 Jul 21.

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• Seners P, Turc G, Oppenheim C, Baron JC. Incidence, causes and predictors of neurological deterioration occurring within 24 h following acute ischaemic stroke: a systematic review with pathophysiological implications. J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):87-94. doi: 10.1136/jnnp-2014-308327. Epub 2014 Jun 26.

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Related Links

• Zhou LX, Ni J.Advances in Branch Atheromatous Disease. Chinese Stroke Journal 2020;15:1342- 1351
• Chinese Stroke Association. Expert consensus on the clinical application of tirofiban in atherosclerotic cerebrovascular disease. Chinese Stroke Journal 2019;14:1034- 1044
• Chinese Society of Neurology, Cerebrovascular disease group of Chinese Society of Neurology. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. Chin J Neurol. 2018;51 9:666-82

MeSH Terms

Conditions

Stroke

Interventions

Tirofiban; Sodium Chloride; Aspirin; Clopidogrel

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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jun Ni, MD

  The office for BRANT study

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Our study is an open label, blinded endpoint trail. The primary outcome should be measured in a blinded manner, and the qualified evaluator is defined as: 1) Attending neurologists or above; 2) Complete the training for mRS score before the initiation of patient enrollment; 3) Blind to the antiplatelet treatment of the participants; and 4) Sign the evaluation when it is completed, and inform the other investigators of the results. All the clinical and safety events will be re-examined by the independent Clinical Event Committee (CEC), who are blinded during all procedures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multi-center, randomized, open label, blinded endpoint, parallel controlled trial

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 14, 2023
• Study Start: November 9, 2023
• Primary Completion: February 26, 2026
• Study Completion: February 26, 2026
• Last Updated: April 15, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

CN (25)