Intra-Arterial Tenecteplase Following Endovascular Thrombectomy for Large Vessel Occlusion Stroke (TNK-FLOW)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Intra-arterial Tenecteplase; Drug: Intra-arterial Saline

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health Neurosciences Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intra-arterial Tenecteplase; Following endovascular thrombectomy for large vessel occlusion stroke one-time dose of intra-arterial Tenecteplase (0.125 mg/kg, maximum dose 12.5 mg) will be delivered over 5-10 seconds by the treating neuro-interventionalist through a microcatheter positioned as close as possible to the residual thrombus or as distal as possible in the originating vessel, per the discretion of the neuro-interventionalist.	Drug: Intra-arterial Tenecteplase; One-time dose of intra-arterial tenecteplase post-thrombectomy
Placebo Comparator: Intra-arterial Saline; Following endovascular thrombectomy for large vessel occlusion stroke one-time dose of saline (0.9% NaCl solution) will be delivered over 5-10 seconds by the treating neuro-interventionalist through a microcatheter positioned as close as possible to the residual thrombus or as distal as possible in the originating vessel, per the discretion of the neuro-interventionalist.	Drug: Intra-arterial Saline; One-time dose of intra-arterial saline post-thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with Change in Symptomatic Intracranial Hemorrhage	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.	Hour 36
Participants with Parenchymal Hematoma Type 1	Number of participants with parenchymal hematoma type 1	24 Hours
Participants with Parenchymal Hematoma Type 2	Number of participants with parenchymal hematoma type 2	24 Hours
30-Day Mortality Count	Number of patients expired	Day 30
90-Day Mortality Count	Number of patients expired	Day 90
Number of Grade 3 Adverse Events	Total number of grade 3 adverse events	Hour 24
Number of Grade 3 Adverse Events	Total number of grade 3 adverse events	Day 5
Number of Grade 3 Adverse Events	Total number of grade 3 adverse events	Day 30
Number of Grade 3 Adverse Events	Total number of grade 3 adverse events	Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving early neurological improvement	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	Hour 24
Proportion of subjects achieving delayed neurological improvement	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	Day 30, Day 90
Ordinal Modified Rankin Scale score	Modified Rankin scale scores range from 0-6. Higher score indicates greater disability.	Day 90
Participants with Change in Modified Rankin Scale Score 0-2 Points	Number of participants with change in Modified Rankin Scale score of 0-2 points or return to baseline modified Rankin scale score.	Day 90
Participants with Change in Modified Rankin Scale Score 0-1 Points	Number of participants with change in Modified Rankin Scale score of 0-1 points or return to baseline modified Rankin scale score.	Day 90
Participants with Change in Modified Rankin Scale Score 0-3 Points	Number of participants with change in Modified Rankin Scale score of 0-3 points or return to baseline modified Rankin scale score.	Day 90
Change in Infarct Volume	Change in infarct volume on follow up CT or MRI	Hour 24
Barthel Index Score	Number of participants with Barthel Index score ≥ 95.	Day 90
Median EuroQol-5-Dimension (EQ-5D) Index	Median EuroQol-5-Dimension (EQ-5D) index has a score range of -0.573 to 1. Higher score indicates better quality score.	Day 90

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Rahul Karamchandani, MD, Atrium Health Neurosciences Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: stroke; blood clot; brain hemorrhage
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Embolism and Thrombosis; Pathological Conditions, Signs and Symptoms; Ischemic Stroke; Stroke; Thrombosis; Intracranial Hemorrhages; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Tenecteplase
• Other Study ID Numbers: IRB00121066; 40010317 (Other Identifier: Genentech, Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No