Not Yet RecruitingPhase 3

Effects of Butylphthalide Enhanced With Tenecteplase on Neurological Function in Mild Disabling Acute Ischemic Stroke

1,062 participantsStarted 2026-02-01

Plain-language summary

Abstract Background Intravenous thrombolysis is the cornerstone of early treatment for acute ischemic stroke (AIS), but some still have a poor prognosis, especially in patients with mild disabling stroke. Tenecteplase (TNK), a novel thrombolytic agent with favorable pharmacokinetic profiles, and butylphthalide (NBP), a multi-targeted neuroprotective drug, have shown promising efficacy in separate clinical applications. However, evidence for their combined use in mild disabling AIS is lacking. Aim To determine whether TNK combined with NBP can improve functional outcomes compared with TNK monotherapy in patients with mild disabling AIS who receive thrombolysis within 4.5 hours of onset. Design BENEFIT-2 is a prospective, multicenter, randomized, double-blind, active-controlled trial. Eligible patients are randomized 1:1 to receive either TNK plus NBP (combination group) or TNK plus placebo (control group) via stratified block randomization. The combination group receives sequential NBP sodium chloride injection (25mg/100ml, twice daily for 7 days) and oral NBP soft capsules (0.2g, three times daily) until day 14; the control group receives matching placebos. Eligibility criteria include age 18-80 years, onset time ≤4.5 hours, NIHSS score 2-5 with disabling manifestations (hemianopia, aphasia, or limb weakness), and pre-stroke modified Rankin Scale (mRS) score ≤1. Study outcomes The primary outcome is the proportion of patients with mRS score 0-1 at 90±7 days. Secondary outcomes include changes in NIHSS score, recurrence of ischemic stroke, composite vascular events, quality of life (assessed by EQ-5D scale), and ischemic penumbra salvage rate. Safety outcomes include symptomatic intracranial hemorrhage (sICH), vascular death, all-cause death, and adverse events within 90 days. Discussion BENEFIT-2 is the first large-scale randomized trial to evaluate the synergistic effect of "vascular recanalization + neuroprotection" in mild disabling AIS. By combining TNK and NBP, this study aims to fill the evidence gap and provide a new therapeutic option to improve functional recovery in this specific population.

Who can participate

Age range

18 Years – 80 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 1\. Age 18-80 years, regardless of gender. * 2\. Clinically diagnosed with acute ischemic stroke and meets the criteria for tenecteplase intravenous thrombolysis. * 3\. Onset of the current stroke within 4.5 hours. * 4\. Clinical diagnosis of minor ischemic stroke with a NIHSS score of 2-5, accompanied by persistent unilateral limb weakness or speech symptoms, defined as a score ≥1 on either the language item or any one limb item of the NIHSS * 5\. Pre-stroke mRS score ≤1. * 6\. The subject or their legal representative is able and willing to sign the informed consent form. Exclusion Criteria: * 1\. History of intracranial hemorrhage. * 2\. Patients who have received or plan to undergo mechanical thrombectomy. * 3\. History of major head trauma or stroke within the past 3 months. * 4\. Known severe liver/kidney dysfunction or patients receiving dialysis (severe liver dysfunction: ALT/AST \>3 times the upper limit of normal; severe kidney dysfunction: serum creatinine \>3.0 mg/dl \[265.2 μmol/L\] or GFR \<30 ml/min/1.73 m²). * 5\. Systolic blood pressure \<90 mmHg or \>220 mmHg. * 6\. Patients with bradycardia (heart rate \<60 beats/min) or sick sinus syndrome. * 7\. History of drug/food allergy or known allergy to the components of the study drugs. * 8\. Patients treated with drugs containing butylphthalide after stroke onset. * 9\. History of congenital/acquired hemorrhagic diseases, coagulation factor deficiency, or thrombocytopenic diseases. * 10\.…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Proportion of patients with Modified Rankin Scale score 0-1 (scores 0 = fully asymptomatic to 6 = death)

Timeframe: From enrollment to the end of treatment at 90 days

Trial details

NCT IDNCT07369999

SponsorXiangya Hospital of Central South University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2029-03-01

Contact for this trial

Qiaoling Tang, MD

18867408758 228111051@csu.edu.cn

View on ClinicalTrials.gov More Mild Disabling Acute Ischemic Stroke trials