Intra-Arterial Tenecteplase Administration Post-Endovascular Recanalization in Acute Anterior Circulation Ischemic Stroke: A Randomized Controlled Trial

The primary objective is to determine whether supplementary intra‑arterial administration of tenecteplase after successful endovascular recanalization of anterior circulation acute ischemic stroke improves functional outcome, measured as the proportion of patients achieving a modified Rankin Scale score of 0–1 at 90 ± 15 days, reflecting the potential for a higher rate of excellent recovery. Secondary objectives include:

• assessment of the proportion of patients with a very good outcome (mRS 0–2) at 90 ± 15 days, recanalization grade, neurological symptom burden, activities of daily living, cognitive status, and health‑related quality of life;
• evaluation of the shift in mRS distribution at 90 days;
• determination of absolute and normalized change in NIHSS at 24 ± 6 hours post‑randomization;
• measurement of EQ‑5D‑5L score at 90 ± 15 days;
• assessment of MoCA score at 90 ± 15 days;
• exploratory analysis of infarct volume.

The trial enrolled adult patients diagnosed with acute ischemic stroke due to large‑vessel occlusion of the anterior circulation, confirmed by imaging and catheter angiography, who achieved successful endovascular recanalization (eTICI ≥ 2b50) within 24 hours of symptom onset. Eligible participants were required to have a pre‑stroke modified Rankin Scale score of 0–1, a baseline NIH Stroke Scale score between 4 and 25, and an ASPECTS of ≥6 on non‑contrast CT (or ≥5 on diffusion‑weighted MRI). Both male and female subjects were included, and the eligibility criteria allowed enrollment of vulnerable individuals. Age criteria required participants to be 18 years or older. The sponsor did not provide information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The LOCAL trial is a phase‑4, randomized, double‑blind, placebo‑controlled, parallel‑group study evaluating intra‑arterial administration of tenecteplase after successful endovascular recanalization in patients with acute ischemic stroke due to anterior‑circulation large‑vessel occlusion. Eligible participants (age ≥ 18 years, NIHSS 4–25, ASPECTS ≥ 6 on CT or ≥ 5 on DWI, pre‑stroke mRS 0–1, onset‑to‑procedure < 24 h, confirmed occlusion and eTICI ≥ 2b50) undergo a screening visit for eligibility confirmation, imaging, and baseline assessments. Upon meeting criteria, subjects are randomized 1:1 to receive either tenecteplase (6.25 mg intra‑arterial) or matching placebo administered immediately after thrombectomy. Study visits consist of the baseline administration (day 0), in‑hospital safety assessments (days 1–3), a discharge assessment, followed by outpatient follow‑up at 30 ± 5 days and a primary efficacy evaluation at 90 ± 15 days, during which the modified Rankin Scale outcome is recorded. Participant involvement therefore spans approximately three months. Early termination may occur if recanalization is not achieved, if a serious adverse event related to the investigational product arises, if protocol violations are identified, or if the participant withdraws consent. Recruitment began on 15 January 2026 and is planned through 31 January 2029.

The investigational product is Metalyse 5 000 units (25 mg) powder for solution for injection, containing the active substance tenecteplase. It is supplied as a solution for injection and administered intra‑arterially at a dose of 6.25 mg immediately following successful endovascular recanalization of an anterior circulation ischemic stroke. A single dose is given per participant; no repeat dosing is planned. Administration is performed by the interventional team under sterile conditions, and the volume of reconstituted solution is recorded in the case report form.

The control arm utilizes a matching Tenecteplase Placebo, presented as a solution for injection with no active ingredient. The placebo is administered intra‑arterially using the same volume, dose timing, and procedural steps as the active product to maintain blinding. Both study treatments are delivered once per procedure, and compliance is monitored by documenting the administration time, route, and complete infusion of the assigned study medication. Observation for immediate adverse events is conducted for at least 30 minutes post‑infusion, and any deviations from the dosing protocol are reported according to the trial’s safety monitoring procedures.

Efficacy will be evaluated by determining the proportion of participants achieving an excellent clinical outcome, defined as a score of 0–1 on the modified Rankin Scale at 90 days (±15 days) after the intra‑arterial tenecteplase administration.

The mRS assessment will be performed by trained investigators using the standard validated questionnaire at the specified follow‑up visit. The primary efficacy analysis will compare the proportion of patients with mRS 0–1 between the tenecteplase and placebo groups.