Safety and Efficacy of Anisodine Hydrobromide in Patients With Ischemic Stroke Undergoing Endovascular Treatment
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 92
- 试验地点
- 20
- 主要终点
- Incidence of Predefined Safety Events
研究概览
简要总结
This study is an investigator-initiated Phase 1b clinical trial employing an open-label, non-randomized, dose-escalation design. The primary objective is to evaluate the safety and tolerability of the investigational intervention and to determine the recommended dose for subsequent clinical studies.
详细描述
This study is an investigator-initiated, prospective, multicenter Phase Ib clinical trial designed to evaluate the safety, tolerability, and dose feasibility of anisodine hydrobromide administered in patients with acute ischemic stroke undergoing endovascular therapy. The trial adopts an open-label, non-randomized, dose-escalation design to identify the maximum tolerated dose (MTD) and to determine the recommended Phase II dose (RP2D).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 80 years.
- •Imaging-confirmed anterior-circulation large-vessel occlusion involving the intracranial internal carotid artery, the middle cerebral artery M1 segment, or the proximal M2 segment or a dominant M2 branch. A dominant M2 branch was defined as an M2 branch supplying ≥50% of the middle cerebral artery territory.
- •Eligible for and planned to undergo endovascular treatment (EVT) within 24 hours according to current clinical practice.
- •National Institutes of Health Stroke Scale (NIHSS) score ≥6 at baseline.
- •Alberta Stroke Program Early CT Score (ASPECTS) ≥6 on baseline noncontrast CT.
- •Pre-stroke modified Rankin Scale (mRS) score of 0 to
- •Provision of written informed consent by the participant or the participant's legally authorized representative.
排除标准
- •Evidence of intracranial hemorrhagic disease on head CT, including hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, or subarachnoid hemorrhage.
- •History of congenital or acquired bleeding disorders, coagulation factor deficiency, thrombocytopenic disorders, or other clinically significant hemorrhagic conditions.
- •Vascular anatomy expected to preclude successful endovascular treatment because of excessive tortuosity or other technical reasons.
- •Known allergy to iodinated contrast agents.
- •Pregnant or breastfeeding women, or women planning pregnancy during the study period or within 90 days after enrollment.
- •Known hypersensitivity to anisodine hydrobromide or a history of severe intolerance after prior exposure.
- •Presence of clinical conditions that may be worsened by anticholinergic drugs, including but not limited to angle-closure glaucoma, urinary retention or benign prostatic hyperplasia with dysuria, or paralytic ileus.
- •Severe arrhythmia or hemodynamic instability, including but not limited to tachyarrhythmia requiring cardioversion, recurrent syncope due to arrhythmia, vasopressor-dependent hypotension, or persistent hypotension.
- •Severe psychiatric disorder, dementia, or impaired consciousness that would preclude informed consent or protocol-required follow-up.
- •Malignant tumor or other severe systemic disease with an expected survival of less than 90 days.
- •Participation in another interventional clinical study within 30 days before enrollment, or current participation in another interventional clinical study.
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
研究组 & 干预措施
Anisodine Hydrobromide 1.5 mg
Participants receive anisodine hydrobromide 1.5 mg per dose intravenously twice daily for 7 consecutive days in addition to standard endovascular therapy. The first dose is initiated before vascular recanalization; however, administration of the study drug must not delay EVT or other standard endovascular procedures. The study drug is diluted in 0.9% sodium chloride solution and infused over approximately 60 minutes.
干预措施: Anisodine Hydrobromide (Drug)
Anisodine Hydrobromide 1.0 mg
Participants receive anisodine hydrobromide 1.0 mg per dose intravenously twice daily for 7 consecutive days in addition to standard endovascular therapy. The first dose is initiated before vascular recanalization; however, administration of the study drug must not delay EVT or other standard endovascular procedures. The study drug is diluted in 0.9% sodium chloride solution and infused over approximately 60 minutes.
干预措施: Anisodine Hydrobromide (Drug)
Anisodine Hydrobromide 2.5 mg
Participants receive anisodine hydrobromide 2.5 mg per dose intravenously twice daily for 7 consecutive days in addition to standard endovascular therapy. The first dose is initiated before vascular recanalization; however, administration of the study drug must not delay EVT or other standard endovascular procedures. The study drug is diluted in 0.9% sodium chloride solution and infused over approximately 60 minutes.
干预措施: Anisodine Hydrobromide (Drug)
Anisodine Hydrobromide 2.0 mg
Participants receive anisodine hydrobromide 2.0 mg per dose intravenously twice daily for 7 consecutive days in addition to standard endovascular therapy. The first dose is initiated before vascular recanalization; however, administration of the study drug must not delay EVT or other standard endovascular procedures. The study drug is diluted in 0.9% sodium chloride solution and infused over approximately 60 minutes.
干预措施: Anisodine Hydrobromide (Drug)
结局指标
主要结局
Incidence of Predefined Safety Events
时间窗: Within 8 days after the first administration
The primary safety outcome is the incidence of prespecified safety events occurring within 8 days after the first administration of the study drug. Prespecified safety events include: (1) symptomatic intracranial hemorrhage, defined as any intracranial hemorrhage confirmed on neuroimaging in conjunction with neurological deterioration, operationalized as an increase of at least 4 points in the NIHSS score; (2) death from any cause; and (3) any other serious adverse event, excluding the foregoing events, that is adjudicated by the Data Monitoring Committee (DMC) to be definitely, probably, or possibly related to the study drug.
次要结局
- Early Neurological Deterioration(Within 24 hours after treatment initiation)
- Infarct Volume(Day 8)
- Functional Outcome (Modified Rankin Scale)(Day 90)
- Symptomatic Intracranial Hemorrhage(Within 8 days after the first administration)
- Intracranial Hemorrhage(Within 8 days after the first administration)
- All-cause Mortality(Within 90 days after the first administration)
研究者
Ji Xunming,MD,PhD
Professor of Neurology, Xuanwu Hospital, Capital Medical University
Capital Medical University