Intra-arterial tenecteplase to improve small-vessel blood flow after mechanical clot removal
Intra-Arterial Tenecteplase to Improve the Microvascular Hemodynamics After Mechanical Thrombectomy
This study will try a single weight-based intra-arterial dose of tenecteplase after successful mechanical thrombectomy to improve microvascular blood flow in adults with anterior large-vessel ischemic stroke.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Pennsylvania Academic / other |
| Drugs / interventions | lecanemab |
| Locations | 1 site (Philadelphia, Pennsylvania) |
| Trial ID | NCT06904911 on ClinicalTrials.gov |
What this trial studies
This is a prospective, single-arm, open-label pilot trial enrolling 20 adults with anterior circulation large-vessel occlusion who achieve successful recanalization (mTICI ≥ 2b) with standard mechanical thrombectomy. After thrombectomy each participant receives a single weight-based intra-arterial dose of tenecteplase and microvascular flow is quantified using pre- and post-drug digital angiography with syngo iFlow. Secondary assessments include 24-hour reperfusion imaging, final infarct volume at 72 hours, short-term NIHSS changes, and 90-day modified Rankin Scale functional outcome. The design is intended to provide preliminary mechanistic and safety data on targeted thrombolysis to improve microvascular reperfusion.
Who should consider this trial
Good fit: Adults (≥18) with acute anterior circulation large-vessel occlusion treated with mechanical thrombectomy who achieve mTICI ≥ 2b, have NIHSS ≥ 6, ASPECTS ≥ 6, and can receive intra-arterial tenecteplase within 24 hours of stroke onset.
Not a fit: Patients with posterior circulation strokes, large early infarcts (ASPECTS < 6), inability to achieve adequate recanalization (mTICI < 2b), or treatment beyond 24 hours are unlikely to benefit from this intervention.
Why it matters
Potential benefit: If successful, targeted intra-arterial tenecteplase could increase microvascular reperfusion after thrombectomy, potentially reducing final infarct size and improving neurological outcomes.
How similar studies have performed: Adjunct intra-arterial thrombolysis is relatively novel with limited prior data, although systemic tenecteplase has shown promise in some acute ischemic stroke trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patient/legally authorized representative has signed the Informed Consent Form * At least 18 years of age * Ability to comply with the study protocol, in the investigator's judgment * Acute ischemic stroke attributed to anterior circulation large vessel occlusion (of the internal carotid artery or first segment of the middle cerebral artery based on CTA, MRA, or catheter angiogram) being treated with mechanical thrombectomy * NIHSS ≥ 6 at the initiation of endovascular therapy (arterial puncture) * Time from stroke onset to IA-TNK administration \< 24 hours. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline * ASPECTS ≥ 6 on pre-MT CT imaging * If treated \> 6 hours from stroke onset, CTP imaging must demonstrates favorable mismatch profile (based on RAPID processing: infarct core \<70 mL, mismatch ratio ≥ 1.8 and mismatch volume ≥ 15 mL) * Qualifying neuroimaging (CT and CTP, if applicable) must be obtained \<120 minutes prior to arterial puncture. Exclusion Criteria: * Current participation in another investigational drug or device study * Known hypersensitivity or allergy to any ingredients of tenecteplase * Active internal bleeding * Known bleeding diathesis (Alzheimer's patients taking lecanemab) * Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \> 1.7 * Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban) * Treatment with a thrombolytic within the last 3 months prior to randomization, inclusive of intravenous thrombolysis during the index stroke. * Baseline platelet count \< 100,000/microliter (results must be available prior to treatment) * Baseline blood glucose \> 400 mg/dL (22.20 mmol/L) * Baseline blood glucose \< 50 mg/dL needs to be normalized prior to randomization * Intracranial or intraspinal surgery or trauma within 2 months * Other serious, advanced, or terminal illness (investigator's judgment) or life expectancy is less than 6 months * History of acute ischemic stroke in the last 90 days * History of hemorrhagic stroke * Presumed septic embolus; suspicion of bacterial endocarditis * Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed * Pregnant * Systolic BP \>185 mmHg or diastolic BP \>110 mmHg, refractory to treatment * Suspicion of aortic dissection * Known allergy to iodine or iodinated contrast * Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram * Renal failure as defined by a serum creatinine \> 3.0 mg/dl or GFR \< 30 * Known intracranial neoplasm * GI bleeding within the past 21 days * Pre-existing medical or neurological disease that will confound the neurological or functional evaluations * Premorbid (prior to the index stroke) modified Rankin Scale (mRS) score ≥ 3 Additional neuroimaging exclusion criteria: * ASPECTS \<6 on pre-MT CT imaging * Acute intracranial hemorrhage or contrast extravasation on CT before or immediately after MT (prior to study drug administration) * Significant mass effect with midline shift on non-contrast CT before or immediately after MT * Cervical or intracranial stent placement during endovascular therapy * Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA, MRA, or catheter angiography
Where this trial is running
Philadelphia, Pennsylvania
- Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Principal investigator: Christopher Favilla, MD — University of Pennsylvania
- Study coordinator: Nichole Gallatti
- Email: Nichole.gallatti@pennmedicine.upenn.edu
- Phone: 215-349-8651
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.