Tenecteplase plus Thrombectomy versus Thrombectomy Alone in Patients with Large Core Ischemic Stroke: A Multicentre Randomized Controlled Trial

The primary objective is to evaluate the efficacy of combining intravenous thrombolysis with tenecteplase and thrombectomy compared to thrombectomy alone regarding the 3-month functional outcome in patients with large vessel occlusion stroke involving large cores. 5

Secondary objectives include:

• Comparison of the rate of good 3-month functional outcome within subgroups, including treatment setting, ASPECTS score (very large versus large cores), and time from symptom onset.
• Assessment of clinical outcomes, specifically early neurological improvement via NIHSS score, 3-month functional independence, distribution of mRS scores, and one-year functional independence or independent ambulation.
• Evaluation of radiological outcomes, including recanalisation rates using eTICI scores and the mean change in infarct volume.
• Analysis of safety outcomes, including early neurological worsening, intracranial hemorrhage based on the Heidelberg Bleeding Classification, 3-month and 1-year mortality, and serious adverse events.
• Comparison of the incremental cost-utility ratio.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients diagnosed with large core large vessel occlusion (LVOS). Eligible participants include individuals aged 18 years or older with a modified Rankin Scale (mRS) score of 0 to 1 prior to the event. The population includes both male and female subjects. Inclusion requires an anterior circulation LVOS eligible for mechanical thrombectomy within 24 hours of onset, or an unknown onset presenting with a diffusion weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch. Specific criteria for a large core involve an Alberta Stroke Program Early CT Score (ASPECTS) of 2 to 5 or specific core volume measurements on magnetic resonance imaging (MRI) or perfusion computed tomography (CT).

This multicentre, open-label randomized controlled trial is designed to evaluate the efficacy of combining intravenous thrombolysis with tenecteplase and thrombectomy versus thrombectomy alone in patients experiencing a large ischemic stroke. The study follows a PROBE design with blinded endpoint assessment. Eligible participants include adults with an anterior circulation large vessel occlusion (LVOS) presenting with a large infarct core within 9 hours of symptom onset or those with a DWI-FLAIR mismatch in cases of unknown onset. The primary objective is to assess the rate of good functional outcome at 3 months, defined by a modified Rankin scale (mRS) score of 0-3. Secondary endpoints include neurological improvement, recanalization rates using eTICI scores, and safety outcomes such as intracranial hemorrhage. The trial involves a screening phase to confirm eligibility, followed by the intervention and subsequent follow-up visits to monitor clinical and radiological outcomes. Total participant involvement extends through the assessment of 3-month and 1-year functional status. The study is estimated to conclude by May 2029.

The experimental treatment consists of tenecteplase, provided as Metalyse 5,000 units (25 mg) in the form of a powder for solution for injection. The administration is conducted via an intravenous bolus at a dose of 25 mg.

The control arm involves thrombectomy alone as the standard-of-care procedure. This study evaluates the efficacy of combining the experimental medication with thrombectomy compared to the use of thrombectomy as a monotherapy in patients presenting with a large ischemic stroke.

The primary efficacy endpoint is the rate of good functional outcome, characterized by independent ambulation, measured at 3 months using a modified Rankin scale (mRS) score of 0-3. Assessment of these scores will be performed by certified raters blinded to the treatment arm and baseline characteristics via in-person interview or telephone.

Secondary clinical outcomes include:

• Early neurological improvement, defined as a decrease of ≥ 8 points on the NIHSS score or an NIHSS score ≤ 1 at day 1.
• 3-month functional independence (mRS score ≤ 2) and the distribution of 3-month mRS scores.
• One-year independent ambulation (mRS score ≤ 3) and one-year functional independence (mRS score ≤ 2).

Radiological outcomes consist of:

• Recanalisation rates, defined by extended Treatment In Cerebral Ischemia (eTICI) scores of 2b50/2b67/2c/3, 2c/3, and 3 during the first angiographic run, after the first pass, and at the end of the procedure.
• The mean change in infarct volume from baseline at day 1.

Safety assessments involve monitoring for early neurological worsening, defined as a ≥ 4-point increase in the NIHSS score within 24 hours due to ischemic stroke. Additional safety measures include the evaluation of intracranial hemorrhage (ICH) and symptomatic ICH using the Heidelberg Bleeding Classification, as well as 3-month and 1-year mortality, adverse events, and serious adverse events. The incremental cost-utility ratio will also be evaluated.