Efficacy and Safety of Intravenous Tenecteplase versus Standard of Care in Patients with Acute Ischemic Stroke Presenting >4.5 Hours from Last Known Well with Salvageable Tissue

The primary objective is to evaluate the superiority of intravenous tenecteplase (0.25 mg/kg, maximum 25 mg) compared to standard of care in achieving an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at Day 90, in patients with acute ischemic stroke. This population includes individuals with a last known well time exceeding 4.5 hours, including wake-up stroke cases, who present with imaging evidence of salvageable ischemic tissue. 5, 4

Secondary objectives include the assessment of:

• Safety of tenecteplase in this clinical setting.
• Efficacy regarding key functional outcomes.

This clinical trial involves 999 participants diagnosed with acute ischemic stroke. The study population consists of male and female patients aged between 18 and 64 years. Eligible individuals must have experienced a stroke affecting the supratentorial circulation, with a time elapsed since being last known well of more than 4.5 hours, including cases of wake-up stroke. Inclusion requires a pre-stroke mRS score of 1 or less and evidence of salvageable brain tissue identified via magnetic resonance imaging or computed tomography. The participants are selected based on these clinical and imaging parameters.

This Phase III, prospective, randomized, open-label, blinded endpoint assessment study is designed to evaluate the efficacy and safety of tenecteplase administered via intravenous bolus compared to the standard of care. The research focuses on patients diagnosed with acute ischemic stroke, including wake-up stroke, where the time since the patient was last known well exceeds 4.5 hours and imaging demonstrates salvageable ischemic tissue. Following the screening visit to confirm eligibility via MRI or CT, participants are randomized to receive either the investigational product or standard treatment. The primary endpoint is the achievement of an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at Day 90. Secondary endpoints include neurological improvement, symptomatic intracranial hemorrhage, and all-cause mortality. The study involves clinical assessments throughout the follow-up period, concluding with an end-of-study evaluation at 90 days post-randomization.

The experimental medication consists of tenecteplase, provided as a powder for solution for injection. The administration involves a single intravenous bolus at a dose of 0.25 mg/kg, not to exceed a maximum of 25 mg.

The comparator treatment is the standard of care administered to participants diagnosed with acute ischemic stroke.

The primary efficacy endpoint is the achievement of an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0–1 at Day 90. The assessment of acute ischemic stroke efficacy also includes several secondary endpoints. These include the ordinal mRS score at Day 90, the rate of mRS 0–2 at Day 90, and death from any cause within 90 days.

Additional secondary assessments involve:

• Early neurological improvement, characterized by a reduction in the 24-hour National Institutes of Health Stroke Scale (NIHSS) score of ≥8 or a value of 0/1.
• Incidence of symptomatic intracranial hemorrhage (sICH) at 36 hours, as defined by SITS-MOST criteria or ECASS III criteria.