Edaravone Dexborneol sublingual tablets for acute small-vessel ischemic stroke

Treatment of Acute Ischemic Stroke With Edaravone Dexborneol Sublingual Tablets in Small Vessel Disease: A Randomized, Double-Blind, Placebo-Controlled Study

This trial will test whether taking Edaravone Dexborneol sublingual tablets twice daily helps adults aged 30–80 who recently had a small subcortical ischemic stroke.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 30 Years to 80 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: lecanemab
• Locations: 1 site (Beijing)
• Trial ID: NCT06674460 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial enrolling about 600 participants with MRI-confirmed recent small subcortical infarcts. Participants are randomized 1:1 to receive Edaravone Dexborneol sublingual tablets (30 mg edaravone + 6 mg dexborneol) or matching placebo twice daily for 24 weeks, followed by a 28-week follow-up for a total of 52 weeks. The primary outcome is a hierarchical composite at week 24 including all-cause mortality, mRS ≥2, recurrent stroke, and changes in cognitive scores (MoCA and VaDAS-Cog). Secondary outcomes include additional functional and cognitive measures at 24 and 52 weeks and MRI markers such as white matter hyperintensities, new infarctions, and microbleeds.

Who should consider this trial

Good fit: Adults 30–80 years old with an MRI-confirmed recent small subcortical infarct (≤20 mm), Fazekas WMH score ≥2, symptom onset within 3 weeks, pre-stroke mRS ≤1, no prior dementia, and able to complete cognitive testing would be ideal candidates.

Not a fit: Patients with large cortical or hemorrhagic strokes, symptom onset beyond 3 weeks, pre-existing dementia or significant pre-stroke disability, or other contraindications are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could lower death, disability, recurrent stroke, and cognitive decline after small-vessel ischemic stroke.

How similar studies have performed: Prior trials of Edaravone Dexborneol (for example the TASTE-SL trial) showed improved 90-day functional outcomes after acute ischemic stroke, but its specific benefit for small vessel disease remains to be confirmed.

Eligibility criteria

1\. Inclusion Criteria:

1. Age: Between 30 and 80 years .
2. MRI-confirmed recent small subcortical infarct (RSSI): A lesion in the small penetrating artery territory, detected as DWI hyperintensity and ADC hypointensity, with a maximum axial diameter ≤20 mm.
3. White Matter Hyperintensity (WMH) Burden: Fazekas score ≥2 (total score range: 0-6).
4. Time from Stroke Onset: ≤3 weeks from symptom onset to randomization.
5. Pre-stroke Functional Status: Modified Rankin Scale (mRS) ≤1 before the index stroke.
6. Cognitive Function: No prior diagnosis of cognitive impairment or dementia.
7. Education Level: At least primary school education and capable of completing cognitive assessments as judged by the investigator.
8. Contraception Requirements:Women of childbearing potential and male participants with female partners of childbearing potential must agree to use effective contraception during the study and 30 days after the last dose of the investigational drug.Female participants must have a negative pregnancy test before enrollment.
9. Informed Consent: Participants or their legal representatives must voluntarily sign an informed consent form (ICF).

2\. Exclusion Criteria:

1. Intracranial Hemorrhagic Diseases: Evidence of hemorrhagic stroke, epidural hematoma, subarachnoid hemorrhage, or other bleeding disorders detected by head imaging (MRI/CT).However, hemorrhagic transformation may be assessed by the investigator for potential inclusion.
2. Severe Consciousness Disturbance: NIHSS item 1a score \>1 (indicative of significant impairment in consciousness).
3. Cortical Infarcts or Other Brain Abnormalities:Co-existing cortical infarcts, hydrocephalus, or other non-vascular white matter diseases (e.g., multiple sclerosis, carbon monoxide poisoning-related leukoencephalopathy).
4. Severe Carotid Artery Stenosis: Requiring surgical intervention (\>50% stenosis).
5. Systemic Conditions Affecting Cognition:Endocrine disorders, vitamin deficiencies, systemic autoimmune diseases that can cause cognitive impairment.
6. Neurological Disorders Associated with Cognitive Decline:CNS infections, Creutzfeldt-Jakob disease, primary Parkinson's disease, epilepsy, brain tumors, or severe traumatic brain injury.
7. Pre-existing Severe Psychiatric Disorders:Diagnosed with major depressive disorder, vascular cognitive impairment, Alzheimer's disease, Parkinson's disease dementia, Lewy body dementia, frontotemporal dementia, or any cognitive dysfunction unrelated to stroke.
8. Severe Physical Disability or Language Impairment:Severe hemiplegia or aphasia that significantly affects cognitive assessment.
9. Use of Cognitive-Enhancing Medications:Within 4 weeks prior to screening, including but not limited to:Cholinesterase inhibitors (donepezil, rivastigmine, galantamine), NMDA receptor antagonists (memantine),Other neuroprotective agents (sodium oligomannate, lecanemab)
10. Severe Liver or Kidney Dysfunction:Active liver disease (acute hepatitis, chronic active hepatitis, cirrhosis) or ALT/AST \>2× ULN.
11. Severe renal impairment (serum creatinine \>1.5× ULN).
12. Life Expectancy \<1 year due to severe systemic diseases.
13. Contraindications to MRI:Participants with MRI-incompatible implants, severe claustrophobia, or inability to undergo MRI.
14. Known Allergies:History of hypersensitivity to Dexborneol, natural borneol, edaravone, or any excipients (e.g., mannitol, copovidone, microcrystalline cellulose, silica, magnesium stearate).
15. Pregnancy and Lactation:Pregnant or lactating women, or those planning pregnancy during the study period.
16. Participation in Other Clinical Trials:Enrolled in another clinical trial within the last 30 days.
17. Other Investigator-Determined Factors:Any other medical, psychological, or social condition that, in the investigator's judgment, makes the patient unsuitable for participation.

Where this trial is running

Beijing

• Peking Union Medical College Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: YiCheng Zhu, Doctor

Conditions Cerebral Small Vessel Disease; Ischemic Stroke; sublingual edaravone dexborneol; cerebral small vessel disease; acute ischemic cerebral small vessel disease; cognition