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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anisodine Hydrobromide 1.0 mg | Experimental | 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. |
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| Anisodine Hydrobromide 1.5 mg | Experimental | 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. |
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| Anisodine Hydrobromide 2.0 mg | Experimental | 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. |
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| Anisodine Hydrobromide 2.5 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anisodine Hydrobromide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Within 8 days after the first administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xunming Ji, MD/PhD | Contact | 01083198962 | jixm@ccmu.edu.cn | |
| Chuanjie Wu, MD | Contact | 01083199439 | wuchuanjie@ccmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xuanwu Hospital, Capital Medical University | Not yet recruiting | Beijing | None Selected | 100053 | China |
Related data will be shared if full study protocol and statistical analysis plan are provided with reasonable design.
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C012183 | anisodine |
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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.
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| Within 24 hours after treatment initiation |
| Infarct Volume | Infarct volume measured on cranial computed tomography (CT) at Day 8, expressed in milliliters (mL). | 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). | Day 90 |
| Symptomatic Intracranial Hemorrhage | Incidence of symptomatic intracranial hemorrhage confirmed by imaging and associated with neurological deterioration (increase of ≥4 points in NIHSS). | Within 8 days after the first administration |
| Intracranial Hemorrhage | Incidence of any intracranial hemorrhage detected by imaging within 8 days after the first administration. | 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. | Within 90 days after the first administration |
| Anji County People's Hospital | Recruiting | Huzhou | Zhejiang | 313300 | China |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |