Butylphthalide for Brain Edema After Endovascular Treatment

Efficacy and Safety of Butylphthalide in Improving Cerebral Edema After Endovascular Treatment in Patients With Acute Anterior Circulation Large Vessel Occlusion: A Multicenter, Double-Blind, Double-Dummy, Randomized Controlled Trial

This is a prospective, multicenter, randomized controlled clinical study aimed at evaluating the efficacy of butylphthalide in improving the severity of cerebral edema and prognosis in patients with acute anterior circulation large vessel occlusion after endovascular treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Butylphthalide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kaibin Huang, PhD; Phone Number: +86 15915751065; Email: hkb@smu.edu.cn
• Study Contact Backup: Name: Suyue Pan, PhD; Phone Number: +86 02062787648; Email: pansuyue@smu.edu.cn

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China
      • Dongguan People's Hospital
      • Contact: Yangkun Chen
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
      • Contact: Suyue Pan; Phone Number: +86 0206278764; Email: pansuyue@smu.edu.cn
    • Guangzhou, Guangdong, China
      • The Fourth Affiliated Hospital of Guangzhou Medical University
      • Contact: Jianbin Zhong
    • Heyuan, Guangdong, China
      • Heyuan People's Hospital
      • Contact: Zhenqin Jiang
    • Qingyuan, Guangdong, China
      • Qingyuan People's Hospital
      • Contact: Xianglin Chen
    • Shaoguan, Guangdong, China
      • Yuebei People's Hospital
      • Contact: Junbin Chen
  • Hainan
    • Haikou, Hainan, China
      • The Second Affiliated Hospital of Hainan Medical University
    • Haikou, Hainan, China
      • Haikou People's Hospital
      • Contact: Guoshuai Yang
    • Haikou, Hainan, China
      • Hainan Provincial Hospital of Traditional Chinese Medicine
      • Contact: Guohu Weng
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • Ganzhou People's Hospital
      • Contact: Xianghong Liu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Time from onset to randomization within 24 hours.
3. Confirmed occlusion of the internal carotid artery or the M1 segment of the middle cerebral artery by digital subtraction angiography (DSA).
4. NIHSS score ≥10 at onset, or NIHSS score >8 at 1 hour post-procedure (for those able to cooperate with NIHSS assessment), or CT-ASPECTS score 3-7 immediately post-procedure.
5. Received endovascular treatment with successful reperfusion (mTICI ≥2b).
6. Signed informed consent form by the subject or their legally authorized representative.

Exclusion Criteria:

1. Pre-stroke modified Rankin Scale (mRS) score ≥2.
2. Immediate post-procedure CT indicating PH2 hemorrhagic transformation or subarachnoid hemorrhage.
3. Immediate post-procedure CT indicating cerebral herniation or planned decompressive craniectomy.
4. History or evidence of intracerebral hemorrhage, subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm, or brain tumor.
5. Evidence (clinical or radiological) of concurrent infarction in the contralateral cerebral hemisphere that, in the investigator's judgment, may affect functional prognosis.
6. Clinical or radiological evidence of vertebral or basilar artery occlusion.
7. History of severe renal impairment (e.g., on dialysis) or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²; severe hepatic disease or alanine aminotransferase (ALT) >3× the upper limit of normal, or total bilirubin >2× the upper limit of normal.
8. Use of butylphthalide within 7 days prior to enrollment.
9. Known allergy to butylphthalide.
10. Pregnancy.
11. Breastfeeding women who do not agree (or whose legally authorized representative does not allow) to discontinue breastfeeding during the study drug administration period and for 7 days thereafter.
12. Participation in other purely observational stroke studies, or expected survival <6 months unrelated to the current stroke, or unlikely to comply with follow-up requirements.
13. Currently receiving another investigational drug with the same or similar mechanism of action as the study drug.
14. Any condition that, in the investigator's opinion, makes the subject unsuitable for participation in the study.

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	Drug: Placebo; For patients in the placebo group, Placebo Injection was administered immediately after randomization, 100 ml per dose, intravenously, twice daily, for at least 7 days, continuing until discharge or day 14.
Experimental: Butylphthalide	Drug: Butylphthalide; For patients in the butylphthalide group, Butylphthalide and Sodium Chloride Injection was administered immediately after randomization, 100 ml per dose, intravenously, twice daily, for at least 7 days, continuing until discharge or day 14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta cerebrospinal fluid	Change from baseline in cerebrospinal fluid	72hours after the stroke onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of modified Rankin Scale (mRS) scores	Shift analysis of mRS scores at 90 days (range 0-6).	90 days after the stroke onset
Midline shift distance	Maximum distance of midline shift (in millimeters) measured on axial CT or MRI.	72 to 96 hours after onset
Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage associated with neurological deterioration (increase in NIHSS ≥4 points) confirmed by CT or MRI.	72hours after the stroke onset
NWU	Net water uptake assessed by CT	72hours after the stroke onset
CED grade	Cerebral edema grade assessed by CT	72hours after the stroke onset
rHV	Relative hemispheric volume ratio assessed by CT	72hours after the stroke onset
Malignant cerebral edema	Defined as the presence of cerebral edema with mass effect on cranial CT or MRI within 48 to 96 hours after symptom onset, including midline shift ≥ 5 mm and/or compression of ventricles or cisterns.	48 to 96 hours after onset
Early neurological deterioration	Defined as an increase of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS; range 0-42, with higher scores indicating worse outcome) within 7 days post-treatment.	Within 7 days post-treatment
Decompressive craniectomy	The subject underwent decompressive craniectomy due to clinical necessity.	Within 7 days post-treatment
Infarct volume	Infarct volume assessed by computed tomography (CT) or magnetic resonance imaging (MR)	48-96hours after the stroke onset
Modified Rankin Scale of 0 to 2 points	Modified Rankin Scale (mRS; range 0-6, with higher scores indicating worse outcome) score of 0 to 2 points.	90 days after the stroke onset

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prognosis; Acute Ischemic Stroke; Endovascular therapy; Cerebral edema; Butylphthalide
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Brain Edema; 3-n-butylphthalide
• Other Study ID Numbers: NFEC-2026-105

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