Acute Disease, Ischemic Stroke
Conditions
Keywords
Stroke, TNK, Thrombolytic
Brief summary
The study objective is to evaluate the safety and efficacy of Intra arterial (IA) Tenecteplase (TNK) as an adjunctive therapy in acute ischemic stroke (AIS) patients with large vessel occlusions (LVO) in the anterior circulation of Internal Carotid Artery (ICA), Middle Cerebral Arteries (M1 and M2) who achieve a reperfusion grade of Modified Treatment in Cerebral Ischemia Scale (mTICI) 2b or higher post-mechanical thrombectomy using Food and Drug Administration (FDA) approved devices.
Interventions
DRUGtenecteplase
Patients treated with standard of care mechanical thrombectomy (MT) that achieved mTICI 2b or higher revascularization. Patients will be randomized into one of two arms: IA TNK or control.
Sponsors
ProMedica Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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. Alberta Stroke Program Early CT Score (ASPECTS) Score ≥6 on baseline Non-contrast Head CT (NCCT) 4. Post-mechanical thrombectomy with ≤5 device passes and mTICI grade 2b or higher. 5. Ability to obtain signed informed consent prior to randomization from LAR or Subject
Exclusion criteria
1. Premorbid modified Rankin scale (mRS) score \>1 2. Imaging evidence of hemorrhage or mass effect at baseline 3. Platelet count \<100,000 4. Active hemorrhagic diathesis, or known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency 5. Active anticoagulation treatment with novel oral anticoagulant (NOACs) taken within the last 48 hours, or INR \>1.7 6. Patients requiring active treatment with dual antiplatelet agents (e.g. proximal cervical carotid artery stenting) 7. Pregnant or lactating 8. Previous known allergy to TNK 9. Major surgery in past 30 days 10. Patient is on or requires dialysis 11. History of intracranial hemorrhage or serious head trauma at any time 12. Any condition in the opinion of the enrolling physician that would preclude the patient from participating 13. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation 14. Severe, uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) that is refractory to treatment 15. History of acute ischemic stroke in the last 60 days and/or has received previous treatment with a thrombolytic within the last 90 days 16. Presumed septic embolus; suspicion of bacterial endocarditis 17. Suspicion of aortic dissection 18. Intracranial neoplasm 19. Any terminal medical condition with life expectancy less than 6 months 20. Concurrent enrollment in another trial that could confound the results of this study 21. Patient is unlikely to return for 90-day follow-up. 22. Intravenous tissue plasminogen activator (tPA) administered concurrently with Intra-arterial TNK
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint- Modified Rankin Scale (mRS) | 90 days (+/- 30 days) post treatment. | Proportion of patients with Modified Rankin Scale (mRS) 0-1 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). |
| Primary Safety Endpoint- Incidence of Intracranial hemorrhage and Neurologic Worsening | 24 hours (+/-12 hours) post treatment. | Incidence of any intracranial hemorrhage and neurologic worsening of at least 4 points on the National Institute of Health Stroke Scale (NIHSS) associated with a Parenchymal hematoma, Type 2 (PH2) brain hemorrhage, according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria, within 24 (±12) hours from randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal Modified Rankin Scale (mRS) | 90 days (+/-30 days) post treatment. | Ordinal mRS at 90 day. 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). |
| Functional Independence | 90 days (+/- 30 days) post treatment. | Proportion of patients with functional independence, defined as a mRS of 0-2 at 90 days. |
| Final Revascularization Grade | Immediate post treatment. | Final revascularization grade at end of IA treatment among those with less than mTICI 3 prior to IA-TNK administration. |
| Mortality rate at 90 days | Mortality rate at 90-days (+/- 30 days) post treatment. | Mortality rate at 90-days |
| Mortality Rate at discharge | Day 6 (+/-1 day) or Discharge post treatment. | Mortality rate at discharge. |
| Infarct Volume Post Procedure | 24 hours (+/- 12 hours) post treatment. | Infarct volume on post-procedure follow-up scans performed at 24 ± 12 hours following mechanical thrombectomy. |
| Asymptomatic Intracranial hemorrhage | 24 hours (+/- 12 hours) post treatment. | Incidence of any asymptomatic intracranial hemorrhage |
| Mean Number of Boluses | Immediate post procedure. | Mean number of boluses to achieve improvement in reperfusion to mTICI 2c and mTICI 3 among those without mTICI3 prior to IA-TNK administration. |
Countries
United States
Contacts
CONTACTSyed Fazal Zaidi, MD
CONTACTTanya Siddiqui
Outcome results
None listed