Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).