Acute Ischemic Stroke
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled clinical trial (SLEDAIS) involving 1,040 patients with acute ischemic stroke (AIS) who require inter-hospital transfer for potential endovascular therapy. The study aims to evaluate the efficacy and safety of sublingual Edaravone Dexborneol tablets administered in the ultra-early stage (within 6 hours of symptom onset) during the critical inter-hospital transfer window. Patients will be randomly assigned in a 1:1 ratio to receive either sublingual Edaravone Dexborneol (a loading dose of 4 tablets initially, followed by 1 tablet twice daily for 13 days) or a matching placebo. The primary efficacy endpoint is the functional outcome assessed by the modified Rankin Scale (mRS) score at 90 days. The primary safety endpoint is the mortality rate at 90 days. This study seeks to provide high-quality evidence for neuroprotection during the transfer period, potentially improving functional recovery for stroke patients.
Interventions
Edaravone Dexborneol is a novel neuroprotective agent combining edaravone (a free radical scavenger) and dexborneol (an anti-inflammatory component) in a 5:1 ratio. In this study, participants in the experimental group will receive a loading dose of 4 sublingual tablets (each containing edaravone 30mg + dexborneol 6mg, total: edaravone 120mg + dexborneol 24mg) within 10 minutes after randomization during inter-hospital transfer. From day 2 to day 14, participants will receive 1 tablet twice daily. The sublingual formulation dissolves within 5 minutes, allowing rapid absorption through the sublingual venous plexus and bypassing hepatic first-pass effect. This high initial loading dose aims to rapidly establish therapeutic concentrations before endovascular therapy to provide neuroprotection during the critical transfer window.
DRUGPlacebo
Matching placebo sublingual tablets identical in appearance, smell, and packaging to the active drug. Participants will receive a loading dose of 4 placebo tablets (each containing 60μg dexborneol, a trace amount solely for maintaining blinding with no expected therapeutic effect) within 10 minutes after randomization. From day 2 to day 14, participants will receive 1 placebo tablet twice daily. The placebo is designed to be indistinguishable from Edaravone Dexborneol tablets to maintain the double-blind design.
Sponsors
Xinqiao Hospital of Chongqing
Simcere Pharmaceutical Group Co., LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 80 years (inclusive). * Time from last known normal to arrival at the first hospital is within 6 hours. * Clinical and imaging diagnosis of acute ischemic stroke, with a Los Angeles Motor Scale (LAMS) score ≥ 4, or occlusion of the internal carotid artery, M1/M2 segment of the middle cerebral artery, V4 segment of the vertebral artery, or basilar artery confirmed by CTA/MRA at the first or target hospital. * ASPECTS score ≥ 6 on non-contrast head CT at the first hospital. * Clinically assessed as planned for immediate transfer to a target hospital for evaluation of endovascular therapy (final decision on whether to perform EVT is made by the neuro-interventionist at the target hospital based on imaging and clinical status). * Written informed consent signed by the patient or their legal representative.
Exclusion criteria
* Allergy to contrast agents, nickel, titanium, or their alloys. * Known allergy to dexborneol, edaravone, or excipients. * Pre-stroke modified Rankin Scale (mRS) score ≥ 2. * Patients receiving intravenous thrombolysis alone. * Severe impairment of consciousness (e.g., GCS score \< 8) or inability to cooperate with sublingual administration. * Severe hepatic or renal insufficiency (e.g., ALT/AST \> 3 times the upper limit of normal, Cr \> 2 times the upper limit of normal). * Estimated inter-hospital transfer time \> 3 hours. * Pregnant or lactating women. * Arterial tortuosity and/or other arterial diseases where the thrombectomy device is expected to be unable to reach the target vessel. * Brain tumors with mass effect on imaging (except small meningiomas). * Currently participating in other drug clinical trials. * History of neurological or psychiatric diseases that hinder the assessment of neurological function. * Any late-stage disease with an expected life expectancy \< 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS) Score at 90 Days | 90 days | Functional outcome assessed by the modified Rankin Scale (mRS) at 90 days post-randomization. The mRS is an ordinal scale ranging from 0 (no symptoms) to 6 (death), used to evaluate the degree of disability or dependence in daily activities. |
| Mortality Rate at 90 Days | 90 days | All-cause mortality rate within 90 days post-randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infarct Volume at 36 Hours | 36 hours | Infarct volume (ml) measured by non-contrast CT or MRI-DWI at 36 hours post-procedure. |
| NIHSS Score at Discharge | 5-7 days or discharge | National Institutes of Health Stroke Scale (NIHSS) score assessed at 5-7 days or at hospital discharge, whichever comes first. |
| Proportion of Patients With mRS 0-1 at 90 Days | 90 days | Percentage of patients achieving excellent functional outcome (mRS score 0-1, indicating no symptoms or symptoms but no disability) at 90 days. |
| Proportion of Patients With mRS 0-2 at 90 Days | 90 days | Percentage of patients achieving functional independence (mRS score 0-2, indicating no to mild disability but able to care for self) at 90 days. |
| EQ-5D-5L Score at 90 Days | 90 days | Health-related quality of life assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire at 90 days. |
| Incidence of Symptomatic Intracranial Hemorrhage at 36 Hours | 36 hours | Incidence of symptomatic intracranial hemorrhage (sICH) assessed by Heidelberg criteria at 36 hours post-procedure. |
| Incidence of Any Intracranial Hemorrhage at 36 Hours | 36 hours | Proportion of patients with any type of intracranial hemorrhage (including hemorrhagic infarction and parenchymal hematoma) at 36 hours. |
| Incidence of Non-Intracranial Hemorrhage Complications | 90 days | Incidence of non-intracranial bleeding complications within 90 days, including gastrointestinal bleeding, urinary tract bleeding, oral or nasal mucosal bleeding, and subcutaneous hematoma. |
| Incidence of Non-Hemorrhagic Serious Adverse Events | 90 days | Incidence of non-hemorrhagic serious adverse events (SAEs) within 90 days. |
Countries
China
Contacts
CONTACTZhongming Qiu, MD
Outcome results
None listed