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

April 3, 2024 updated by: Peking Union Medical College Hospital

Efficacy and Safety of Tirofiban in Patients With Acute Branch Atheromatous Disease (BAD)- Related Stroke (BRANT)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

516

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 101300
        • Not yet recruiting
        • Beijing Shunyi hospital
        • Contact:
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Jun Ni
        • Contact:
    • Hebei
      • Baoding, Hebei, China, 071051
        • Recruiting
        • The second hospital of Baoding
        • Contact:
      • Chengde, Hebei, China, 067024
      • Chifeng, Hebei, China, 024099
        • Recruiting
        • Affiliated Hospital of Chifeng University
        • Contact:
      • Hengshui, Hebei, China, 053099
        • Recruiting
        • Hengshui People's Hospital
        • Contact:
      • Tangshan, Hebei, China, 063000
        • Recruiting
        • North China University of Science and Technology Affiliated Hospital
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150001
        • Recruiting
        • The Second Affiliated Hospital of Harbin Medical University
        • Contact:
          • Xiaotong Kong, MD
    • Henan
      • Shangqiu, Henan, China, 476005
        • Recruiting
        • The First People's Hospital of Shangqiu
        • Contact:
      • Xinxiang, Henan, China, 453100
        • Recruiting
        • The First Affiliated Hospital of Xinxiang Medical Unversity
        • Contact:
      • Zhengzhou, Henan, China, 450014
        • Not yet recruiting
        • The Second Affiliated Hospital Of Zhengzhou University
        • Contact:
    • Jiangsu
      • Xuzhou, Jiangsu, China, 221009
        • Not yet recruiting
        • Xuzhou Central Hospital
        • Contact:
          • Chen Wang, MD
    • Jilin
      • Meihekou, Jilin, China, 135022
        • Recruiting
        • Meihekou Central Hospital
        • Contact:
          • Rui Wang, MD
    • Shandong
      • Dongying, Shandong, China, 257099
        • Recruiting
        • Shengli Oilfield Central Hospital
        • Contact:
      • Jinan, Shandong, China, 250013
    • Sichuan
      • Deyang, Sichuan, China, 618099
        • Recruiting
        • Deyang People's Hospital
        • Contact:
          • Juan Wang, MD
      • Mianyang, Sichuan, China, 621099
        • Recruiting
        • Mianyang Central Hospital
        • Contact:
          • Wen Zhou, MD
      • Yibin, Sichuan, China, 644000
        • Not yet recruiting
        • The Second People's Hospital of Yibin
        • Contact:
          • Daofeng Chen, MD
      • Yibin, Sichuan, China, 644000
        • Recruiting
        • The First People's Hospital of Yibin
        • Contact:
          • Yanping Wu, MD
    • Tianjing
      • Tianjing, Tianjing, China, 300211
        • Recruiting
        • The Second Hospital of Tianjin Medical University
        • Contact:
          • Yudong Wang, MD
    • Tibet
      • Lhasa, Tibet, China, 850000
        • Recruiting
        • Tibet Autonomous Region People's Hospital
        • Contact:
          • Yaxiong Hu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirofiban group
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
Tirofiban, a GPIIb/IIIa receptor inhibitor. Intravenous administration.
Other Names:
  • Tirofiban Hydrochloride and Sodium Chloride Injection
Active Comparator: Standard antiplatelet therapy group
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
Aspirin. Oral administration.
Drug: Clopidogrel tablet
Clopidogrel. Oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Excellent functional outcome
Time Frame: 90 days

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Excellent functional outcome
Time Frame: 7 days
modified Rankin Scale score: 0-1
7 days
Early neurological deterioration
Time Frame: 7 days of randomization
The presence of END is determined by an increase of ≥ 4 points in the NIHSS or an increase of ≥2 points in the NIHSS motor score. In addition, NIHSS motor score refers to bilateral upper and lower extremity mobility scores. The baseline NIHSS score for the calculation of END is the first clinician-evaluated and recorded NIHSS score after onset. The time frame for post-randomization END is within 7 days of randomization.
7 days of randomization
NIHSS score
Time Frame: 7 days and 90 days
The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
7 days and 90 days
Barthel index score
Time Frame: 7 days and 90 days
The Barthel Index (BI) is tool to measure the extent to which somebody can function independently and has mobility in activities of daily living (ADL), including 10 aspects: feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. Higher score indicates better performance in activities of daily living.
7 days and 90 days
Ischemic stroke
Time Frame: 7 days and 90 days
Number of participants with new-onset ischemic stroke, confirmed by senior neurologists and the Clinical Event Committee.
7 days and 90 days
Stroke
Time Frame: 7 days and 90 days
Number of participants with new-onset ischemic or hemorrhagic stroke, confirmed by senior neurologists and the Clinical Event Committee.
7 days and 90 days
TIA
Time Frame: 7 days and 90 days
Number of participants with new-onset transient ischemic attack (TIA), confirmed by senior neurologists and the Clinical Event Committee.
7 days and 90 days
Composite endpoint
Time Frame: 7 days and 90 days
Number of participants with new-onset stroke, myocardial Infarction, or all-cause death, confirmed by the Clinical Event Committee.
7 days and 90 days
Serious adverse events
Time Frame: 7 and 90 days
Serious adverse events
7 and 90 days
Adverse events
Time Frame: 7 and 90 days
Adverse events
7 and 90 days
All-cause death
Time Frame: 7 and 90 days
All-cause death
7 and 90 days
Changes in hemoglobin
Time Frame: 48 hours
Blood test of the count of hemoglobin, g/L
48 hours
Changes in the count of red blood cell
Time Frame: 48 hours
Blood test of the count of red blood cell, 10^12/L
48 hours
Changes in the count of white blood cell
Time Frame: 48 hours
Blood test of the count of white blood cell, 10^9/L
48 hours
Changes in the count of platelets
Time Frame: 48 hours
Blood test of the count of platelets, 10^9/L
48 hours
Changes in alanine transaminase
Time Frame: 48 hours
Serum biochemical test for alanine transaminase
48 hours
Changes in aspartate aminotransferase
Time Frame: 48 hours
Serum biochemical test for aspartate aminotransferase
48 hours
Changes in direct bilirubin
Time Frame: 48 hours
Serum biochemical test for the concentration of direct bilirubin
48 hours
Changes in indirect bilirubin
Time Frame: 48 hours
Serum biochemical test for the concentration of indirect bilirubin
48 hours
Changes in concentration of Na
Time Frame: 48 hours
Serum biochemical test for the concentration of sodium, mmol/L
48 hours
Changes in the concentration of K
Time Frame: 48 hours
Serum biochemical test for the concentration of potassium, mmol/L
48 hours
Changes in the concentration of creatinine
Time Frame: 48 hours
Serum biochemical test for creatinine
48 hours
Changes in the concentration of albumin
Time Frame: 48 hours
Serum biochemical test for albumin
48 hours
Changes in the urinary occult blood
Time Frame: 48 hours
The test of urine blood (BLD). Negative or positive.
48 hours
Changes in the fecal occult blood
Time Frame: 48 hours
The test of occult blood (Occult blood, OB). Negative or positive
48 hours
Proportion of Major bleeding
Time Frame: 7 days and 90 days
Proportion of major bleeding defined by the PLATO criteria.
7 days and 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Pharmaron (Chengdu) Clinical Services Co., Ltd.

Investigators

  • Principal Investigator: Jun Ni, MD, The office for BRANT study

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 9, 2023

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

October 31, 2025

Study Registration Dates

First Submitted

September 7, 2023

First Submitted That Met QC Criteria

September 13, 2023

First Posted (Actual)

September 14, 2023

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAD-RCT202201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data that support the findings of this study are available from the corresponding author on reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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