NCT07230587

Butylphthalide for Long-term Efficacy in Minor Stroke Study

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Long-Term Efficacy of Butylphthalide in Patients With Minor Acute Ischemic Stroke (BLESS)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,200 (estimated)
• Sponsor: Peking Union Medical College Hospital · Academic / Other
• Sex: All
• Age: 40 Years – 80 Years
• Healthy volunteers: Not accepted

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. All-cause mortality 2. Stroke recurrence 3. Modified Rankin Scale (mRS) score ≥2 4. New MRI-confirmed infarcts 5. Change in Montreal Cognitive Assessment (MoCA) score from baseline Secondary outcomes include additional functional, cognitive, and imaging-based assessments at 12 months. This study aims to determine whether butylphthalide can improve long-term functional and cognitive outcomes in patients with minor ischemic stroke, contributing to better secondary stroke prevention strategies.

Detailed description

1. Background and Rationale Minor acute ischemic stroke accounts for a significant proportion of all ischemic strokes and is associated with a substantial risk of recurrent stroke and cognitive impairment. Despite advances in secondary stroke prevention, effective long-term treatments targeting both functional recovery and neuroprotection remain limited. Butylphthalide, a compound originally derived from celery seed, has demonstrated neuroprotective, anti-inflammatory, and microcirculatory-enhancing effects in preclinical and clinical studies. Previous trials have suggested its potential benefits in improving neurological function and preventing stroke progression. The BLESS Trial (Butylphthalide for Long-term Efficacy in Minor Stroke Study) is designed to evaluate the long-term efficacy and safety of butylphthalide in patients with minor acute ischemic stroke, focusing on its impact on functional outcomes, cognitive performance, and neuroimaging markers. 2. Study Design and Methods This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll approximately 1200 participants across 50 sites in China. Participants will be randomized in a 1:1 ratio to receive: Butylphthalide soft capsules (200 mg, three times daily) for 12 months, or Matching placebo for 12 months. Participants will undergo regular follow-ups with comprehensive assessments of clinical, cognitive, and imaging parameters. 3. Primary Outcome Measure A hierarchical composite endpoint assessed at 12 months using the Win Ratio method, prioritizing the following outcomes: * All-cause mortality ②Stroke recurrence ③Modified Rankin Scale (mRS) score ≥2 ④New MRI-confirmed infarcts ⑤Change in Montreal Cognitive Assessment (MoCA) score from baseline 4.Secondary Outcome Measures * All-cause mortality * Recurrent stroke * Modified Rankin Scale (mRS) score ≥2 * MRI-confirmed new infarcts * Composite endpoint of ① + ② + ③ * Composite endpoint of ① + ② + ③ + ④ * Distribution of mRS scores ⑧ Change in MMSE score from baseline * Change in MoCA score from baseline * IADL score ⑪ Change in total Fazekas score of white matter hyperintensities from baseline ⑫ Change in white matter hyperintensity volume from baseline ⑬ Change in DTI parameters from baseline 5\. Statistical Analysis The Win Ratio method will be used for primary endpoint analysis, prioritizing mortality and severe disability outcomes. Secondary outcomes will be analyzed using Cox proportional hazards models, mixed-effects models, and logistic regression as appropriate. A significance level of P \< 0.05 will be considered statistically significant. 6.Study Significance This study aims to determine whether butylphthalide can improve long-term functional and cognitive outcomes in minor stroke patients and provide a novel neuroprotective strategy for secondary stroke prevention. If successful, the findings could influence clinical guidelines for stroke management.

Conditions

• Ischemic Stroke
• Minor Stroke

Interventions

Type	Name	Description
DRUG	Butylphthalide	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
DRUG	Placebo	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.

Timeline

• Start date: 2025-12-01
• Primary completion: 2027-09-01
• Completion: 2028-10-01
• First posted: 2025-11-17
• Last updated: 2025-11-17