Repeat tenecteplase for early ischemic stroke with medium or large vessel blockage

Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2): a Prospective, Randomized, Open Label, Blinded Assessment of Outcome, and Multi-center Study

This trial will try giving a second dose of the clot-busting drug tenecteplase to adults with ischemic stroke from medium or large vessel blockages who still have an occlusion one hour after the first dose and are within 4.5 hours of symptom onset.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 198 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: General Hospital of Shenyang Military Region (other)
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT07375966 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study tests a rescue strategy of repeated intravenous tenecteplase in patients with imaging-confirmed medium or large vessel occlusion who do not show significant improvement one hour after standard thrombolysis. Eligible adults must have received standard-dose IV thrombolysis within 4.5 hours, have measurable deficits (NIHSS ≥4) and acceptable baseline imaging scores (ASPECTS/pc-ASPECTS ≥6 or Pontine-Midbrain Index ≤2). Follow-up vascular imaging at one hour must confirm persistent occlusion and exclude intracranial hemorrhage before administering a second tenecteplase dose. The goal is to increase early recanalization and clinical improvement, particularly where endovascular therapy is not planned or available.

Who should consider this trial

Good fit: Adults (≥18) with acute ischemic stroke due to confirmed medium or large vessel occlusion who received standard IV thrombolysis within 4.5 hours, have NIHSS ≥4 and acceptable baseline imaging, and show persistent occlusion without significant neurological improvement one hour after the first dose.

Not a fit: Patients with small-vessel strokes, those who improved substantially after the first thrombolysis, those with intracranial hemorrhage on follow-up imaging, or those with a planned thrombectomy are unlikely to benefit from a repeat dose.

Why it matters

Potential benefit: If successful, a second dose of tenecteplase could increase early artery reopening and improve recovery for patients who do not respond to the first thrombolysis or who cannot access thrombectomy.

How similar studies have performed: Tenecteplase has been shown to be non-inferior to alteplase for initial thrombolysis, but using a second systemic dose as a rescue for persistent medium or large vessel occlusion is a novel approach with limited previous data.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 year;
* Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received standard-dose intravenous thrombolysis, and with no planned thrombectomy;
* Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
* Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
* No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis;
* Follow-up imaging (CTA or MRA) at 1 hour after the first thrombolysis rules out intracranial hemorrhage and confirms the presence of large or medium vessel occlusion (internal carotid artery, M1-M3 segments of the middle cerebral artery, A1-A3 segments of the anterior cerebral artery, P1-P3 segments of the posterior cerebral artery, basilar artery or V4 segment of the vertebral artery, PICA, AICA, or SCA);
* The second intravenous thrombolysis can be administered within 6 hours of onset;
* First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
* Signed informed consent.

Exclusion Criteria:

* Planed for endovascular treatment;
* Significant white matter hyperintensities (Fazekas score 3);
* Any coagulation abnormality before the first thrombolysis, including INR \> 1.5;
* Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
* Pregnancy；
* Allergy to the investigational drug(s)；
* Comorbidity with other serious diseases;
* Participating in other clinical trials within 3 months;
* Patients not suitable for the study considered by researcher.

Where this trial is running

Shenyang, Liaoning

• Lu Wang — Shenyang, Liaoning, China (RECRUITING)

Conditions: Ischemic Stroke