NCT07230587

Brief Summary

This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the long-term efficacy and safety of butylphthalide in patients with minor acute ischemic stroke (BLESS Trial). A total of 1200 participants aged 40 to 80 years with a minor acute ischemic stroke confirmed by MRI will be enrolled. Participants will be randomly assigned in a 1:1 ratio to receive butylphthalide or placebo for 12 months. The primary outcome is a hierarchical composite endpoint assessed at 12 months, including:

  1. 1.All-cause mortality
  2. 2.Stroke recurrence
  3. 3.Modified Rankin Scale (mRS) score ≥2
  4. 4.New MRI-confirmed infarcts
  5. 5.Change in Montreal Cognitive Assessment (MoCA) score from baseline

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,200

participants targeted

Target at P75+ for phase_3

Timeline
30mo left

Started Dec 2025

Typical duration for phase_3

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress15%
Dec 2025Oct 2028

First Submitted

Initial submission to the registry

July 14, 2025

Completed
4 months until next milestone

First Posted

Study publicly available on registry

November 17, 2025

Completed
14 days until next milestone

Study Start

First participant enrolled

December 1, 2025

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2027

Expected
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

November 17, 2025

Status Verified

November 1, 2025

Enrollment Period

1.8 years

First QC Date

July 14, 2025

Last Update Submit

November 13, 2025

Conditions

Ischemic StrokeMinor Stroke

Keywords

minor strokeButylphthalide

Outcome Measures

Primary Outcomes (5)

  • All cause mortality

    The number of participants who experience all-cause mortality at 12 months. All-cause mortality includes death from any reason, such as cardiovascular, neurological, or other systemic causes.

    12 months

  • Stroke recurrence

    The number of participants who experience a recurrent stroke within 12 months. Recurrent stroke is defined as a new ischemic or hemorrhagic stroke, confirmed by neurological symptoms lasting ≥24 hours and neuroimaging evidence (MRI or CT)

    12 months

  • Modified Rankin Scale (mRS) Score ≥2

    The proportion of participants with a modified Rankin Scale (mRS) score ≥2 at 12 months. The mRS is a widely used functional outcome measure that assesses the degree of disability or dependence in daily activities following a stroke. The scale ranges from 0 (no symptoms) to 6 (death), with scores of 2 or higher indicating functional dependence.

    12 months

  • New MRI-Confirmed Infarcts

    The number of new infarcts confirmed by MRI at 12 months, compared to baseline. New infarcts are defined as newly developed ischemic lesions identified on diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) sequences. A higher number of new infarcts indicates increased disease progression.

    12 months

  • Change in Montreal Cognitive Assessment (MoCA) Score from Baseline

    The change in Montreal Cognitive Assessment (MoCA) Score from baseline to 12 months. The MoCA is a cognitive screening tool that assesses multiple domains, including attention, concentration, executive function, memory, language, visuospatial skills, abstract thinking, calculation, and orientation. Scores range from 0 to 30, with higher scores indicating better cognitive function.

    12 months

Secondary Outcomes (11)

  • All cause mortality

    12 months

  • Stroke Recurrence

    12 months

  • Distribution of Modified Rankin Scale (mRS) Scores

    12 months

  • New MRI-Confirmed Infarcts

    12 months

  • Change in Mini-Mental State Examination (MMSE) Score from Baseline

    12 months

  • +6 more secondary outcomes

Study Arms (2)

Butylphthalide

EXPERIMENTAL

Butylphthalide 200 mg (oral soft capsules), three times daily for 12 months

Drug: Butylphthalide

Placebo

PLACEBO COMPARATOR

Placebo (matching oral soft capsules), three times daily for 12 months.

Drug: Placebo

Interventions

ButylphthalideDRUG

Butylphthalide (NBP) is a neuroprotective agent derived from celery seed. It has demonstrated potential benefits in improving microcirculation, reducing oxidative stress, and protecting against neuronal injury in ischemic stroke. This study uses butylphthalide soft capsules (200 mg per dose) administered orally, three times daily for 12 months, to evaluate its long-term efficacy and safety in patients with minor acute ischemic stroke

Also known as: 3-n-Butylphthalide, NBP
Butylphthalide
PlaceboDRUG

Matching placebo soft capsules, identical in appearance to butylphthalide capsules, administered orally at a dose of one capsule (200 mg equivalent) three times daily for 12 months. The placebo contains inactive ingredients without pharmacological effects and is used as a control to assess the efficacy and safety of butylphthalide in patients with minor acute ischemic stroke.

Placebo

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age between 40 and 80 years old.
  • NIHSS score 0-5 at the time of stroke diagnosis, with MRI-confirmed acute ischemic infarct.
  • Time from stroke onset to enrollment ≤ 2 weeks.
  • Pre-stroke mRS score ≤ 1.
  • No prior diagnosis of cognitive impairment or dementia.
  • Informed consent must be voluntarily signed by the patient or their legal representative.

You may not qualify if:

  • Based on the TOAST classification, consider cardioembolic stroke, stroke of other determined etiology, or stroke of undetermined etiology.
  • Intracranial hemorrhagic diseases on imaging: hemorrhagic stroke, epidural hematoma, subarachnoid hemorrhage, etc. (If hemorrhagic transformation is present, eligibility is at investigator's discretion.)
  • Carotid artery stenosis \> 50% requiring surgical intervention.
  • Systemic diseases causing cognitive impairment (e.g., endocrine diseases, vitamin deficiency, systemic autoimmune diseases).
  • Neurological disorders causing cognitive impairment, such as CNS infections, Creutzfeldt-Jakob disease, primary Parkinson's disease, traumatic brain injury, epilepsy, brain tumors.
  • Pre-stroke diagnosis of severe psychiatric disorders, including but not limited to depression, non-vascular cognitive impairment, or dementia (e.g., Alzheimer's disease, Parkinson's disease dementia, Lewy body dementia, frontotemporal dementia, drug or alcohol-induced cognitive impairment).
  • Severe hemiplegia and aphasia that significantly affect cognitive assessment.
  • Use of cognitive-enhancing drugs within 4 weeks before screening, including cholinesterase inhibitors (donepezil, rivastigmine, galantamine), NMDA receptor antagonists (memantine), sodium oligomannate (GV-971), or monoclonal antibodies (lecanemab, donanemab, aducanumab).
  • Severe liver disease (e.g., acute hepatitis, active chronic hepatitis, cirrhosis) or ALT/AST \> 2× ULN.
  • Severe kidney disease or renal impairment (serum creatinine \> 1.5× ULN).
  • Coagulation disorders or thrombocytopenia (platelet count \< 100 × 10⁹/L).
  • Severe systemic diseases with an expected survival \< 1 year.
  • Contraindications for MRI or inability to complete MRI scan.
  • Allergy to butylphthalide.
  • Pregnancy, lactation, or planned pregnancy.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (2)

  • Tan Z, Zhao Y, Yang W, He S, Ding Y, Xu A. Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA-Analysis From a Nationwide, Multicenter Registry. Front Neurol. 2021 Sep 22;12:720664. doi: 10.3389/fneur.2021.720664. eCollection 2021.

    PMID: 34630292RESULT

  • Amarenco P, Lavallee PC, Monteiro Tavares L, Labreuche J, Albers GW, Abboud H, Anticoli S, Audebert H, Bornstein NM, Caplan LR, Correia M, Donnan GA, Ferro JM, Gongora-Rivera F, Heide W, Hennerici MG, Kelly PJ, Kral M, Lin HF, Molina C, Park JM, Purroy F, Rothwell PM, Segura T, Skoloudik D, Steg PG, Touboul PJ, Uchiyama S, Vicaut E, Wang Y, Wong LKS; TIAregistry.org Investigators. Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke. N Engl J Med. 2018 Jun 7;378(23):2182-2190. doi: 10.1056/NEJMoa1802712. Epub 2018 May 16.

    PMID: 29766771RESULT

MeSH Terms

Conditions

Ischemic Stroke

Interventions

3-n-butylphthalide

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Central Study Contacts

YiCheng Zhu, Doctor

CONTACT

(+86)01069156380zhuych910@163.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2025

First Posted

November 17, 2025

Study Start

December 1, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

October 1, 2028

Last Updated

November 17, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share