Intra-Arterial Tenecteplase Following Endovascular Thrombectomy for Large Vessel Occlusion Stroke

Overview

The purpose of this study is to determine the safety and feasibility of using intra-arterial Tenecteplase in patients undergoing blood clot extraction for treatment of acute ischemic (non-bleeding) stroke. Intravenous Tenecteplase is FDA-approved to treat patients with an ischemic stroke presenting within the 0-3-hour time window.

Detailed description

The primary objective of this study is to determine the safety and feasibility of intra-arterial Tenecteplase in selected patients with persistent post-thrombectomy hypoperfusion on computed tomography perfusion based on symptomatic intracranial hemorrhage (parenchymal hematoma type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage producing decline from the initial NIHSS of ≥ 4 points) at 24-36 hours.

Interventions

• Drug Intra-arterial Tenecteplase
  One-time dose of intra-arterial tenecteplase post-thrombectomy
• Drug Intra-arterial Saline
  One-time dose of intra-arterial saline post-thrombectomy

Primary outcome measures

• Participants with Change in Symptomatic Intracranial Hemorrhage [Time frame: Hour 36]
• Participants with Parenchymal Hematoma Type 1 [Time frame: 24 Hours]
• Participants with Parenchymal Hematoma Type 2 [Time frame: 24 Hours]
• 30-Day Mortality Count [Time frame: Day 30]
• 90-Day Mortality Count [Time frame: Day 90]
• Number of Grade 3 Adverse Events [Time frame: Hour 24]
• Number of Grade 3 Adverse Events [Time frame: Day 5]
• Number of Grade 3 Adverse Events [Time frame: Day 30]
• Number of Grade 3 Adverse Events [Time frame: Day 90]

Eligibility criteria

Inclusion criteria

• Patient/legally authorized representative has signed the Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Functionally independent (modified Rankin scale 0-2) prior to presentation
• Baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 6
• Clinical syndrome consistent with occlusion of the internal carotid artery (ICA) or proximal middle cerebral artery (MCA), presenting within 4.5- to 24-hours of TLKW
• Evidence of ICA, MCA-M1, or MCA-M2 occlusion on baseline computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA). ICA/MCA tandem occlusions may be enrolled
• Alberta Stroke Program Early Computed Tomography Score ≥ 6 on pre-thrombectomy unenhanced CT as determined by treating neurologist or reading radiologist
• Pre-thrombectomy CTP or MRP with core infarction (cerebral blood flow < 30%) < 70 ml, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 ml (completed within 120 minutes of skin puncture for thrombectomy). If skin puncture occurs more than 120 minutes after the pre-thrombectomy CTP, enrollment may proceed at the PI's discretion.
• Endovascular thrombectomy of ICA, MCA-M1 or MCA-M2 occlusion performed according to local standard of care, defined as at least completing the initial diagnostic angiogram
• CTP performed with RAPID AI AngioFlowTM within 30 minutes of thrombectomy completion
• Modified thrombolysis in cerebral infarction (mTICI) 2b-3 revascularization following endovascular thrombectomy (EVT) (or after initial diagnostic angiogram)
• Presence of Tm > 6 lesion on post-EVT CTP of adequate quality for interpretation in the distribution of the symptomatic occlusion

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 (e.g., Alzheimer's patients taking lecanemab)
• Systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg after EVT, refractory to medical therapy
• 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
• Baseline platelet count < 100,000/mcL (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
• Intracranial malignant neoplasm, arteriovenous malformation, or unsecured aneurysm > 1 cm
• 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
• Acute intracranial hemorrhage on pre-thrombectomy imaging or suspected acute intracranial hemorrhage after EVT
• Acute bilateral strokes on initial imaging
• Multiple acute intracranial occlusions (except ICA/MCA) on initial CTA or MRA
• Significant hemispheric mass effect or any amount of midline shift due to acute stroke
• Placement of cervical carotid or intracranial stent during thrombectomy procedure requiring dual antiplatelet therapy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Atrium Health Neurosciences Institute — Charlotte

Identifiers

NCT: NCT06781385 · IRB00121066 · 40010317

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗