NCT07369999

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

Effects of Butylphthalide Enhanced With Tenecteplase on Neurological Function in Mild Disabling Acute Ischemic Stroke -A Prospective, Multicenter, Randomized, Double-blind, Active-controlled Trial

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,062 (estimated)
• Sponsor: Xiangya Hospital of Central South University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Mild Disabling Acute Ischemic Stroke

Interventions

Type	Name	Description
DRUG	Combination Group	Combination Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, NBP 100 ml (25 mg) is initiated as an intravenous infusion, twice daily (bid), for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP soft capsules (0.2 g, three times daily \[tid\]) will be started on the day of discharge, and continued until Day 14.
DRUG	Control Group	Control Group: TNK 0.25 mg/kg (maximum 25 mg) administered as a single intravenous infusion. Immediately after that, a 100 ml intravenous infusion of NBP placebo (visually identical to NBP) is initiated twice daily (bid) for 7 consecutive days. If the hospitalization duration is less than 7 days, oral NBP placebo soft capsules (visually identical, 0.2 g, three times daily \[tid\]) will be started on the day of discharge and continued until Day 14.

Timeline

• Start date: 2026-02-01
• Primary completion: 2029-03-01
• Completion: 2029-06-30
• First posted: 2026-01-27
• Last updated: 2026-02-12