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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Anisodine 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.
Zhangpu County Hospital
Zhangzhou, Fujian, China
Jiuquan City People's Hospital
Jiuquan, Gansu, China
The Second People's Hospital of Yulin
Yulin, Guangxi, China
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.
Time frame: Within 8 days after the first administration
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.
Time frame: Within 24 hours after treatment initiation
Infarct Volume
Infarct volume measured on cranial computed tomography (CT) at Day 8, expressed in milliliters (mL).
Time frame: Day 8
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).
Time frame: Day 90
Symptomatic Intracranial Hemorrhage
Incidence of symptomatic intracranial hemorrhage confirmed by imaging and associated with neurological deterioration (increase of ≥4 points in NIHSS).
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The First People's Hospital of Shangqiu
Shangqiu, Henan, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
Xuanwu Hospital, Capital Medical University
Beijing, None Selected, China
Zibo Central Hospital
Zibo, Shandong, China
Anji County People's Hospital
Huzhou, Zhejiang, China
Taizhou Enze Medical Center (Group) Enze Hospital
Taizhou, Zhejiang, China
Yueqing People's Hospital
Yueqing, Zhejiang, China
Time frame: Within 8 days after the first administration
Intracranial Hemorrhage
Incidence of any intracranial hemorrhage detected by imaging within 8 days after the first administration.
Time frame: Within 8 days after the first administration
All-cause Mortality
All-cause mortality occurring within 90 days after the first administration of the investigational drug.
Time frame: Within 90 days after the first administration