Acute Ischemic Stroke
Conditions
Keywords
brain hemorrhage, stroke, blood clot
Brief summary
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
One-time dose of intra-arterial tenecteplase post-thrombectomy
DRUGIntra-arterial Saline
One-time dose of intra-arterial saline post-thrombectomy
Sponsors
Genentech, Inc.
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 computed tomography perfusion (CTP) or magnetic resonance perfusion (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) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants with Change in Symptomatic Intracranial Hemorrhage | Hour 36 | Number of participants with symptomatic intracranial hemorrhage (parenchymal hematoma type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage) producing decline from the initial National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 points. |
| Participants with Parenchymal Hematoma Type 1 | 24 Hours | Number of participants with parenchymal hematoma type 1 |
| Participants with Parenchymal Hematoma Type 2 | 24 Hours | Number of participants with parenchymal hematoma type 2 |
| 30-Day Mortality Count | Day 30 | Number of patients expired |
| 90-Day Mortality Count | Day 90 | Number of patients expired |
| Number of Grade 3 Adverse Events | Hour 24 | Total number of grade 3 adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants with Change in Modified Rankin Scale Score 0-3 Points | Day 90 | Number of participants with change in Modified Rankin Scale score of 0-3 points or return to baseline modified Rankin scale score. |
| Median EuroQol-5-Dimension (EQ-5D) Index | Day 90 | Median EuroQol-5-Dimension (EQ-5D) index has a score range of -0.573 to 1. Higher score indicates better quality score. |
| Barthel Index Score | Day 90 | Number of participants with Barthel Index score ≥ 95. |
| Change in Infarct Volume | Hour 24 | Change in infarct volume on follow up CT or MRI |
| Proportion of subjects achieving early neurological improvement | Hour 24 | Proportion of subjects achieving early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) reduction by ≥ 4 points or total NIHSS 0-2 |
| Proportion of subjects achieving delayed neurological improvement | Day 30, Day 90 | Proportion of subjects achieving delayed neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) reduction by ≥ 4 points or total NIHSS 0-2 |
| Ordinal Modified Rankin Scale score | Day 90 | Modified Rankin scale scores range from 0-6. Higher score indicates greater disability. |
| Participants with Change in Modified Rankin Scale Score 0-2 Points | Day 90 | Number of participants with change in Modified Rankin Scale score of 0-2 points or return to baseline modified Rankin scale score. |
| Participants with Change in Modified Rankin Scale Score 0-1 Points | Day 90 | Number of participants with change in Modified Rankin Scale score of 0-1 points or return to baseline modified Rankin scale score. |
Countries
United States
Outcome results
None listed