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

Official title

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

Overview

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.

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).

Interventions

• 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 sequenti

Primary outcome measures

• Incidence of Predefined Safety Events [Time frame: Within 8 days after the first administration]

Secondary outcome measures (6)

• Early Neurological Deterioration [Time frame: Within 24 hours after treatment initiation]
• Infarct Volume [Time frame: Day 8]
• Functional Outcome (Modified Rankin Scale) [Time frame: Day 90]
• Symptomatic Intracranial Hemorrhage [Time frame: Within 8 days after the first administration]
• Intracranial Hemorrhage [Time frame: Within 8 days after the first administration]
• All-cause Mortality [Time frame: Within 90 days after the first administration]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 10 centers

• Zhangpu County Hospital — Zhangzhou
• Jiuquan City People's Hospital — Jiuquan
• The Second People's Hospital of Yulin — Yulin
• The First People's Hospital of Shangqiu — Shangqiu
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou
• Xuanwu Hospital, Capital Medical University — Beijing
• Zibo Central Hospital — Zibo
• Anji County People's Hospital — Huzhou
• … and 2 more centers

Identifiers

NCT: NCT07513233 · HEAL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗