Sublingual Edaravone Dexborneol for Inter-hospital Transfer Acute Ischemic Stroke (SLEDAIS)

Official title

Efficacy and Safety of Sublingual Edaravone Dexborneol for Inter-hospital Transfer Acute Ischemic Stroke: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

Overview

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

• Drug Edaravone dexborneol sublingual tablet
  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 dail
• Drug Placebo
  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 dou

Primary outcome measures

• Modified Rankin Scale (mRS) Score at 90 Days [Time frame: 90 days]
• Mortality Rate at 90 Days [Time frame: 90 days]

Secondary outcome measures (9)

• Infarct Volume at 36 Hours [Time frame: 36 hours]
• NIHSS Score at Discharge [Time frame: 5-7 days or discharge]
• Proportion of Patients With mRS 0-1 at 90 Days [Time frame: 90 days]
• Proportion of Patients With mRS 0-2 at 90 Days [Time frame: 90 days]
• EQ-5D-5L Score at 90 Days [Time frame: 90 days]
• Incidence of Symptomatic Intracranial Hemorrhage at 36 Hours [Time frame: 36 hours]
• Incidence of Any Intracranial Hemorrhage at 36 Hours [Time frame: 36 hours]
• Incidence of Non-Intracranial Hemorrhage Complications [Time frame: 90 days]
• Incidence of Non-Hemorrhagic Serious Adverse Events [Time frame: 90 days]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Xinqiao Hospital and The Second Affiliated Hospital — Chongqing

Publications

• Fu Y, Wang A, Tang R, Li S, Tian X, Xia X, Ren J, Yang S, Chen R, Zhu S, Feng X, Yao J, Wei Y, Dong X, Ling Y, Yi F, Deng Q, Guo C, Sui Y, Han S, Wen G, Li C, Dong A, Sun X, Wang Z, Shi X, Liu B, Fan D. Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial. JAMA Neurol. 2024 Feb 19;81(4):319-26. doi: 10.1001/jamaneurol.2023.5716. Online PMID 38372981

Identifiers

NCT: NCT07682922 · 2026-189-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗