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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Edaravone dexborneol sublingual tablet; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 1040
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhongming Qiu, MD; Phone Number: +86 13236599269; Email: qiuzhongmingdoctor@163.com

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400000
      • Xinqiao Hospital and The Second Affiliated Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	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 double-blind design.
Experimental: Edaravone Dexborneol Group	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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) Score at 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.	90 days
Mortality Rate at 90 Days	All-cause mortality rate within 90 days post-randomization.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct Volume at 36 Hours	Infarct volume (ml) measured by non-contrast CT or MRI-DWI at 36 hours post-procedure.	36 hours
NIHSS Score at Discharge	National Institutes of Health Stroke Scale (NIHSS) score assessed at 5-7 days or at hospital discharge, whichever comes first.	5-7 days or discharge
Proportion of Patients With mRS 0-1 at 90 Days	Percentage of patients achieving excellent functional outcome (mRS score 0-1, indicating no symptoms or symptoms but no disability) at 90 days.	90 days
Proportion of Patients With mRS 0-2 at 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.	90 days
EQ-5D-5L Score at 90 Days	Health-related quality of life assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire at 90 days.	90 days
Incidence of Symptomatic Intracranial Hemorrhage at 36 Hours	Incidence of symptomatic intracranial hemorrhage (sICH) assessed by Heidelberg criteria at 36 hours post-procedure.	36 hours
Incidence of Any Intracranial Hemorrhage at 36 Hours	Proportion of patients with any type of intracranial hemorrhage (including hemorrhagic infarction and parenchymal hematoma) at 36 hours.	36 hours
Incidence of Non-Intracranial Hemorrhage Complications	Incidence of non-intracranial bleeding complications within 90 days, including gastrointestinal bleeding, urinary tract bleeding, oral or nasal mucosal bleeding, and subcutaneous hematoma.	90 days
Incidence of Non-Hemorrhagic Serious Adverse Events	Incidence of non-hemorrhagic serious adverse events (SAEs) within 90 days.	90 days

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: Simcere Pharmaceutical Group Co., LTD

Publications and helpful links

General 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 ahead of print.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: 2026-189-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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