Anisodine Hydrobromide for Patients With Acute Ischemic Stroke Undergoing Endovascular Therapy (HEAL) (HEAL)

Safety and Efficacy of Anisodine Hydrobromide in Patients With Ischemic Stroke Undergoing Endovascular Treatment

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Anisodine Hydrobromide

Detailed Description

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
• Enrollment (Estimated): 92
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chuanjie Wu, MD; Phone Number: 01083199439; Email: wuchuanjie@ccmu.edu.cn
• Study Contact Backup: Name: Xunming Ji, MD/PhD; Phone Number: 01083198962; Email: jixm@ccmu.edu.cn

Study Locations

• China
  • None Selected
    • Beijing, None Selected, China, 100053
      • Not yet recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Chuanjie Wu, MD; Phone Number: 01083199439; Email: wuchuanjie@ccmu.edu.cn
      • Contact: Xunming Ji, MD/PhD; Phone Number: 01083198962; Email: jixm@ccmu.edu.cn
  • Zhejiang
    • Huzhou, Zhejiang, China, 313300
      • Recruiting
      • Anji County People's Hospital
      • Contact: fujian Chen; Phone Number: +86 572 5122905; Email: ajrmyy@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 1.
• Provision of written informed consent by the participant or the participant's legally authorized representative.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Anisodine Hydrobromide; 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.
Experimental: 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.	Drug: Anisodine Hydrobromide; 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.
Experimental: 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.	Drug: Anisodine Hydrobromide; 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.
Experimental: 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.	Drug: Anisodine Hydrobromide; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.	Within 24 hours after treatment initiation

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Neuroprotection; Endovascular Treatment
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; anisodine
• Other Study ID Numbers: HEAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Related data will be shared if full study protocol and statistical analysis plan are provided with reasonable design.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No