Clinical trial NCT06037889: Efficacy and Safety of Tirofiban for Patients With BAD (BRANT)
Official title: Efficacy and Safety of Tirofiban in Patients With Acute Branch Atheromatous Disease (BAD)- Related Stroke (BRANT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Branch Atheromatous Disease
Keywords: Branch atheromatous disease
Tirofiban
Stroke
Treatment Outcome
Magnetic Resonance Imaging
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Pharmaron (Chengdu) Clinical Services Co., Ltd.
First posted: 2023-09-14
Enrollment: 516
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multi-center, randomized, open label, blinded endpoint, parallel controlled trial
Primary purpose: TREATMENT

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.

Detailed description: BRANT study is a multicenter, randomized, open label, blinded endpoint, Parallel controlled trial with the primary null hypothesis that, in patients with acute BAD-related stroke, there is no difference in the proportion of excellent outcome in those treated with intravenous Tirofiban compared with those treated with standard antiplatelet therapy based on guideline when subjects are randomized within 48 hours of stroke onset.

The primary objective is to determine whether intravenous tirofiban (a loading dose of 0.4ug/kg/min\*30min followed by a maintenance dose of 0.1ug/kg/min\*47.5h) is effective in increasing the proportion of excellent functional outcome (mR: 0-1) at 90 days, when initiated within 48 hours of onset. The active comparator is standard antiplatelet therapy based on guideline \[ie, 1) aspirin 150-300 mg qd, OR 2) aspirin 100 mg qd plus clopidogrel 75 mg qd\] for 48 hours.

Patients with acute BAD-related stroke between 18 and 75 years old, who can be randomized within 48 hours of onset, and meet the BAD Diagnostic Imaging Criteria, will be enrolled. All patients will conduct MRI before randomization.

Subjects will be randomized 1:1 (Tirofiban: Standard antiplatelet therapy). The subjects' eligibility will be assessed by site investigator prior to accessing the Randomization Module, which is generated via the dynamic block randomization method. Only certified and trained personnel can access the randomization website, who will get the information of treatment (ie, Tirofiban or standard antiplatelet therapy) after the subject has be determined eligible.

The treatment period is 48 hours for both study groups. A total of 516 eligible patients will be enrolled. Each participant will be followed for 90 days from randomization. The primary outcome will be assessed by well-trained senior neurologists blinded to the treatment. All the clinical and safety events will be re-examined by the Clinical Event Committee (CEC), who are blinded during all procedures.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-75 years old
2. Acute ischemic stroke
3. Time from onset to randomization ≤48h; if onset time is unknown, time from last known well to randomization ≤48h
4. Meet the following BAD Diagnostic Imaging Criteria

   4.1. DWI infarcts: single (isolated) deep (subcortical) infarcts;

   4.2. 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 coronary position; 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;

   4.3. 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 \[DSA\]).
5. Singed informed consent by the patient or legally authorized representatives.

Exclusion Criteria:

1. Transient ischemic attack (TIA)
2. 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;
3. Presence of ≥50% stenosis in extracranial artery in tandem relationship ipsilateral to the lesion;
4. Cardiogenic embolism: atrial fibrillation, myocardial infarction, heart valve disease, dilated cardiomyopathy, infective endocarditis, atrioventricular block disease, heart rate less than 50 beats per minute
5. Have received or plan to receive endovascular therapy or thrombolysis after onset;
6. Stroke of other clear causes, e.g., moyamoya disease, arterial entrapment, vasculitis, etc.
7. modified Rankin Scale ≥2 before onset
8. Use of tirofiban within 1 week before or after onset
9. 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
10. Elevation of ALT or AST more than 1.5 times the upper normal limit;
11. Glomerular filtration rate \<60 ml/min/1.73m\^2
12. Known malignant tumors
13. History of trauma or major surgical intervention within 6 weeks prior to onset
14. History of intracranial hemorrhage
15. Active or recent history(within 30 days prior to onset) of clinical bleeding (e.g., gastrointestinal bleeding)
16. Malignant hypertension (systolic blood pressure \>200 mmHg, or diastolic blood pressure \>120 mmHg)
17. Life expectancy ≤ 6 months
18. Contraindications of 3 T MRI examination
19. Pregnant or lactating women
20. Have participated in another clinical trial within 3 months prior to the date of informed consent, or are participating in another clinical trial.

Primary outcomes:
measure: Excellent functional outcome
timeFrame: 90 days
Secondary outcomes:
measure: Excellent functional outcome
timeFrame: 7 days
measure: Early neurological deterioration
timeFrame: 7 days of randomization
measure: NIHSS score
timeFrame: 7 days and 90 days
measure: Barthel index score
timeFrame: 7 days and 90 days
measure: Ischemic stroke
timeFrame: 7 days and 90 days
measure: Stroke
timeFrame: 7 days and 90 days
measure: TIA
timeFrame: 7 days and 90 days
measure: Composite endpoint
timeFrame: 7 days and 90 days
measure: Proportion of Major bleeding
timeFrame: 7 days and 90 days
measure: Serious adverse events
timeFrame: 7 and 90 days
measure: Adverse events
timeFrame: 7 and 90 days
measure: All-cause death
timeFrame: 7 and 90 days
measure: Changes in hemoglobin
timeFrame: 48 hours
measure: Changes in the count of red blood cell
timeFrame: 48 hours
measure: Changes in the count of white blood cell
timeFrame: 48 hours
measure: Changes in the count of platelets
timeFrame: 48 hours
measure: Changes in alanine transaminase
timeFrame: 48 hours
measure: Changes in aspartate aminotransferase
timeFrame: 48 hours
measure: Changes in direct bilirubin
timeFrame: 48 hours
measure: Changes in indirect bilirubin
timeFrame: 48 hours
measure: Changes in concentration of Na
timeFrame: 48 hours
measure: Changes in the concentration of K
timeFrame: 48 hours
measure: Changes in the concentration of creatinine
timeFrame: 48 hours
measure: Changes in the concentration of albumin
timeFrame: 48 hours
measure: Changes in the urinary occult blood
timeFrame: 48 hours
measure: Changes in the fecal occult blood
timeFrame: 48 hours
Other outcomes:
Locations:
city: Beijing
country: China
facility: Jun Ni
state: Beijing
city: Beijing
country: China
facility: Beijing Shunyi Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: The First Hospital of Tsinghua University
state: Beijing
city: Baoding
country: China
facility: The second hospital of Baoding
state: Hebei
city: Botou
country: China
facility: Botou City Hospital
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Chengde
country: China
facility: Chengde Central Hospital
state: Hebei
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng University
state: Hebei
city: Hengshui
country: China
facility: Hengshui People's Hospital
state: Hebei
city: Tangshan
country: China
facility: North China University of Science and Technology Affiliated Hospital
state: Hebei
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Sanmenxia
country: China
facility: Yellow River SANMENXIA Hospital
state: Henan
city: Shangqiu
country: China
facility: The First People's Hospital of Shangqiu
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical Unversity
state: Henan
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Dongying
country: China
facility: Shengli Oilfield Central Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Deyang
country: China
facility: Deyang People's Hospital
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Yibin
country: China
facility: The First People's Hospital of Yibin
state: Sichuan
city: Yibin
country: China
facility: The Second People's Hospital of Yibin
state: Sichuan
city: Tianjing
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjing
city: Lhasa
country: China
facility: Tibet Autonomous Region People's Hospital
state: Tibet
Study officials:
affiliation: The office for BRANT study
name: Jun Ni, MD
role: PRINCIPAL_INVESTIGATOR
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