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.
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.
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.
Sequential
Anisodine Hydrobromide
DrugAnisodine hydrobromide injection is administered intravenously in addition to standard endovascular therapy for acute ischemic stroke. The investigational drug is diluted in 250 mL of 0.9% sodium chloride solution and infused over approximately 60 minutes. Treatment is given twice daily (BID) for 7 consecutive days, with the first dose initiated prior to vascular recanalization. In this Phase Ib study, four dose levels (1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg per dose) are evaluated using a sequential, cohort-based dose-escalation design to assess safety, tolerability, and dose feasibility. All participants receive standard-of-care endovascular therapy according to current clinical guidelines, including mechanical thrombectomy and/or adjunctive procedures as clinically indicated.
Incidence of Predefined Safety Events
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.
Early Neurological Deterioration
Early neurological deterioration is defined as a worsening in neurological status within 24 hours after the initiation of treatment. Neurological status is quantified using the National Institutes of Health Stroke Scale (NIHSS), a validated clinical instrument for assessing stroke severity. The total score of the NIHSS ranges from a minimum of 0 to a maximum of 42. On this scale, higher scores indicate greater neurological impairment and a worse clinical outcome, whereas a score of 0 represents the absence of detectable neurological deficits.
Infarct Volume
Infarct volume measured on cranial computed tomography (CT) at Day 8, expressed in milliliters (mL).
Functional Outcome (Modified Rankin Scale)
Functional outcome assessed using the modified Rankin Scale (mRS), reported as the distribution of scores ranging from 0 (no symptoms) to 6 (death).
Symptomatic Intracranial Hemorrhage
Incidence of symptomatic intracranial hemorrhage confirmed by imaging and associated with neurological deterioration (increase of ≥4 points in NIHSS).
Click on the lead sponsor to view all of their trials.
