A Dose-Response Controlled Trial of Bevifibatide for Acute Ischemic Stroke

Официальное название

Efficacy and Safety of Bevifibatide Citrate Injection in Patients With Acute Ischemic Stroke Without Large or Medium-Sized Vessel Occlusion: A Single-Center, Randomized, Double-Blind, Dose-Response Controlled Clinical Trial

Обзор

BCAIS-I is a single-center, randomized, double-blind, dose-response controlled clinical Trial, to preliminarily explore the efficacy of two different maintenance doses of bevifibatide citrate injection in improving 90-day neurological outcomes and the incidence of symptomatic intracranial hemorrhage in patients with acute ischemic stroke without large or medium-sized vessel occlusion, aiming to identify a dosing regimen that maintains therapeutic efficacy while minimizing the rates of symptomatic intracranial hemorrhage and serious adverse events, thereby providing dosing evidence for future large-scale randomized controlled trials.

Подробное описание

Bevifibatide is a derivative similar to Eptifibatide, differing by only one amino acid: in the position where Eptifibatide contains high arginine, it is replaced by arginine to form Bevifibatide. Bevifibatide can specifically bind to the GPIIb/IIIa receptor, inhibiting platelet aggregation or adhesion. It also inhibits the integrin receptor αvβ3, thereby suppressing the growth of vascular smooth muscle and playing an important role in preventing arterial re-occlusion. Bevifibatide is a post-marketing product indicated for unstable angina, non-Q wave myocardial infarction, non-ST segment elevation myocardial infarction, and anti-thrombotic therapy during and around percutaneous coronary intervention. Its clinical formulation is an injectable solution for intravenous administration. When Bevifibatide is used in combination with clinical baseline medications, it has a synergistic effect on anti-platelet aggregation. Early oral administration of aspirin and clopidogrel can achieve a rapid synergistic effect on anti-platelet aggregation.

Currently, there are no clinical trials assessing the relationship between the dosage of Bevifibatide and its efficacy in treating acute ischemic stroke. We conduct a single-center, randomized, double-blind, dose-response controlled clinical trial to preliminarily evaluate and compare the effectiveness of conventional dosage and low maintenance dosage of Bevifibatide citrate injection in improving neurological outcomes at 90 days and the incidence of symptomatic intracranial hemorrhage in patients suffering from acute ischemic stroke without large or medium-sized vessel occlusion, thereby determining a relatively safe dosage while maintaining the effectiveness of the medication, and providing a dosage basis for conducting large-sample randomized controlled trials.

Вмешательства

• Препарат Bevifibatide citrate injection
  Bevifibatide citrate injection should be diluted with 0.9% NaCl solution. After the completion of the study drug infusion, if a follow-up cranial NCCT/MRI within 48 hours shows no significant intracranial hemorrhage, all patients will be administered enteric-coated aspirin tablets (100mg, qd) and clopidogrel hydrogen sulfate tablets (75mg, qd) until day 90. All patients will be managed in accordance with the current guidelines for stroke management. The use of low molecular weight heparin for th

Первичные конечные точки

• The modified Rankin Scale (mRS) score [Срок оценки: 90(±7) days]
• Symptomatic intracranial hemorrhage (sICH) [Срок оценки: Within 48 hours]

Вторичные конечные точки (12)

• mRS score 0-1 at 30 days [Срок оценки: 30(±3) days]
• mRS score 0-2 at 30 days [Срок оценки: 30(±3) days]
• mRS score 0-1 at 90 days [Срок оценки: 90(±7) days]
• mRS score 0-2 at 90 days [Срок оценки: 90(±7) days]
• Change of the National Institute of Health Stroke Scale (NIHSS) score from baseline to 72 hours [Срок оценки: 72(±12) hours]
• Change of the NIHSS score from baseline to 6 days [Срок оценки: 6(±1) days]
• Change of the NIHSS score from baseline to 90 days [Срок оценки: 90(±7) days]
• Health-related quality of life [Срок оценки: 90(±7) days]
• Any ICH [Срок оценки: Within 48 hours]
• Mortality [Срок оценки: 90(±7) days]
• Incidence of serious adverse events [Срок оценки: 90(±7) days]
• Incidence of adverse events [Срок оценки: 90(±7) days]

Критерии участия

Критерии включения

• Any of the following presentations of acute ischemic stroke (AIS): ① Within 24 hours of time last known well and ineligible for intravenous thrombolysis (IVT) or endovascular treatment (EVT). ② More than 24 hours and less than 96 hours after time last known well but within 24 hours of ischemic stroke progression \[worsening of ≥ 2 points on the NIHSS\]; and ineligible for IVT or EVT without ICH confirmed by CT scan or MRI. ③ Treated with IVT followed by early neurological deterioration (worse NIHSS by ≥ 4 points) within the first 24 hours after IVT without ICH confirmed by CT scan or MRI. ④ Treated with IVT followed by no neurological improvement (Neurological improvement is defined as decrease in the NIHSS score by ≥ 2 points) from baseline within 4 to 24 hours after IVT without ICH confirmed by CT scan or MRI.
• NIHSS score ≥ 3 immediately prior to trial entry.
• Without visible large or medium intracranial vessel occlusion on CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA). (Qualifying mechanisms are: 1. hypoperfusion caused by arterial stenosis; 2. the initial occluded large or medium artery spontaneously recanalized or recanalized with IVT before the vascular imaging performed; 3. multiple or single distal emboli from cardiac or other sources in arterial branches too small to visualized on CTA or MRA; 4. lacunar infarct due to small vessel occlusion).
• Written informed consent obtained from patients or their legal representatives.

Критерии исключения

• CT or MR evidence of intracranial haemorrhage.
• Pre-morbid disability with a mRS score ≥ 2.
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, sick sinus syndrome, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%.
• Planned treatment with dual antiplatelet therapy within 1week of the index stroke.
• Any history of a primary or other intracerebral (parenchymal) haemorrhage (intraventricular, subarachnoid, subdural, epidural).
• Any untreated or incompletely treated intracranial aneurysm, any intracranial vascular malformation or any intracranial tumour.
• Currently pregnant or lactating, and those planned to conceive.
• Subjects with positive urine HCG test results.
• Known allergy to study medication or concomitant medications.
• Gastrointestinal bleeding, urinary tract bleeding, or other major systemic haemorrhage within 30 days.
• Any major surgery within 6 weeks of the index stroke.
• History of heparin-induced thrombocytopenia.
• Expected lifespan less than 3 months.
• Pre-existing neurological or psychiatric disease that would confound the neurological functional outcome evaluations.
• Any of the following laboratory tests: INR \[International Normalized Ratio\]>2.0, PT>1.3 times normal value, platelet count<100 × 109/L, Hb<10g/dl.
• Systolic pressure greater than 180 mmHg or diastolic pressure greater than 110 mmHg after aggressive treatment.
• Severe renal insufficiency (glomerular filtration rate < 30 ml/min or serum creatinine > 220 μmol/L \[2.5 mg/dl\]).
• History of liver dysfunction (AST/ALT exceeding the upper limit of normal by more than twice) or cirrhosis.
• Arterial tortuosity and/or other arterial diseases that prevent the expected internal thrombectomy device from reaching the target vessel.
• Unlikely to be available for 90-day follow-up.
• Current participation in another treatment clinical trial.
• Other conditions that are not suitable for participation in the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhujiang Hospital of Southern Medical University — Гуанчжоу

Идентификаторы

NCT: NCT06712004 · LC2024ZD032

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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