Adjunctive Intra-arterial Tenecteplase Following Mechanical Thrombectomy Pilot Trial

Study Overview
=================
Brief Summary
-----------------
Prospective, single center, non-randomized, pilot study to assess the feasibility of IA TNK following standard of care mechanical thrombectomy (MT) in patients with AIS. Participants will receive IA TNK after achieving mTICI 2b or 2c reperfusion with standard of care MT. Patients enrolled into the study will be followed for 3 months after treatment with IA TNK.

Detailed Description
-----------------
As current MT technology is not amenable to retrieval of distal occlusions (M3/M4, etc), we hypothesize that IA lytic may play an important role as an adjunctive therapy to open up distal vessels (after the primary LVO has been removed) to achieve complete or near complete reperfusion. In this pilot trial, our goal is to assess the feasibility and safety of IA Tenecteplase (TNK) as an adjunctive therapy following standard of care mechanical thrombectomy (MT) in patients with AIS. A total of 20 patients will be enrolled into the ALLY pilot study.

Official Title
-----------------
Adjunctive Intra-arterial Tenecteplase Following Mechanical Thrombectomy Pilot Trial

Conditions
-----------------
Ischemic Stroke

Intervention / Treatment
-----------------
* Drug: intra-arterial tenecteplase


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Age 18-85 2. Anterior circulation ischemic stroke symptoms with confirmed occlusion (ICA, M1, or M2) on angiogram and mechanical thrombectomy initiated within 24 hours since last known well 3. a. Patients treated less than 6 hours since last known well with ASPECTS >6. b. Patients treated beyond 6 hours since last known well, CT or MRI perfusion scan showing favorable mismatch profile (Target mismatch profile on CT perfusion or MRI (ischemic core volume is <70ml, mismatch ratio is >1.8 and mismatch volume is >15ml) 4. Post-mechanical thrombectomy with ≤5 device passes and mTICI grade 2b or 2c with persistent occlusion(s) in terminal branches not amenable to MT. 5. Signed informed consent Exclusion Criteria: 1. Premorbid modified Rankin scale (mRS) score of 4 or greater 2. Presence of any hemorrhage and/or ASPECT score ≤6 on baseline head CT 3. Platelet count <100,000 4. Known bleeding diathesis 5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency 6. Active anticoagulation treatment with novel oral anticoagulant (NOACs) taken within the last 48 hours, or INR >1.8 7. Patients requiring active treatment with dual antiplatelet agents (e.g. proximal cervical carotid artery stenting) 8. Pregnant or lactating 9. Previous known allergy to TNK 10. Major surgery in past 30 days 11. Patient is on or requires dialysis 12. History of intracranial hemorrhage or serious head trauma at any time 13. Any condition in the opinion of the enrolling physician that would preclude the patient from participating 14. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation 15. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) that is refractory to treatment 16. History of acute ischemic stroke in the last 60 days 17. Presumed septic embolus; suspicion of bacterial endocarditis 18. Suspicion of aortic dissection 19. Intracranial neoplasm 20. Any mass effect 21. Any terminal medical condition with life expectancy less than 6 months 22. Concurrent enrollment in another trial that could confound the results of this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will receive intra-arterial Tenecteplase after achieving mTICI 2b or 2c reperfusion with standard of care mechanical thrombectomy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-arterial Tenecteplase<br>Participants will receive intra-arterial Tenecteplase after achieving mTICI 2b or 2c reperfusion with standard of care MT. | Drug: intra-arterial tenecteplase<br>* intra-arterial drug administered after mechanical thrombectomy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of any intracranial hemorrhage and neurologic worsening | Incidence of any intracranial hemorrhage and neurologic worsening of at least 4 points on the National Institute of Health Stroke Scale (NIHSS), according to the European Cooperative Acute Stroke Study II (ECASS-II) criteria, within 24 hours of treatment with IA TNK | 24 hours post-treatment with intra-arterial Tenecteplase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved reperfusion | Proportion of patients with improved reperfusion (mTICI 2c/3) at end of IA treatment | immediate post-treatment | 
| Improved reperfusion | Proportion of patients with improvement of reperfusion to mTICI 2c, mTICI 3, and mTICI 2c-3. | immediate post-treatment | 
| Ordinal modified Rankin Scale Score | Ordinal modified Rankin Scale Score at 90 days. The mRS is the standard tool to assess neurological outcome in trials with acute severe brain disease. The scale runs from 0-6, running from perfect health without symptoms (= 0) to death (= 6). | 90 days post-treatment | 
| Functional Independence | Proportion of patients with functional independence, defined as a mRS of 0-2 at 90 days | 90 days post-treatment | 
| Final revascularization grade | Final revascularization grade at end of IA treatment using the modified Thrombolysis in Cerebral Infarction (mTICI) grading scale. | immediate post-treatment | 
| Mortality | Mortality rate at discharge | Hospital Discharge (Day 6 post-randomization (+/- 1 day)) | 
| Asymptomatic intracranial hemorrhage | Incidence of any asymptomatic intracranial hemorrhage | 24 hours post-treatment | 
| Mean number of boluses | Mean number of boluses to achieve improvement in reperfusion to mTICI 2c and mTICI 3 | Immediate post-procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thrombolytic, stroke, distal emboli