Acute Ischemic Stroke – TIMELESS

Name: TIMELESS (A PHASE III, PROSPECTIVE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF THROMBOLYSIS IN IMAGING-ELIGIBLE, LATE-WINDOW PATIENTS TO ASSESS THE EFFICACY AND SAFETY OF TENECTEPLASE)

Contact:  Neringa May (CRC, 352-273-6448), Dr. Amita Singh (PI)

Enrolling hours: technically 24/7, still need to work out on call schedule.

Diagnosis: AIS

Inclusion:

  1. Age >=18 years
  2. AIS symptom onset within 4.5 to 24 hours
  3. Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
  4. Functionally independent (mRS 0-2) prior to stroke onset
  5. Baseline NIHSS >=5 and that remains >=5 immediately prior to randomization
  6. Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) by magnetic resonance angiography (MRA) or CTA AND target mismatch profile on CTP or MR perfusion MRP) (ischemic core volume <70 mL, mismatch ratio is >= 1.8 and mismatch volume is >=15 mL)

Exclusion:

  1. Current participation in another investigational drug or device study
  2. Known hypersensitivity or allergy to any ingredients of tenecteplase
  3. Active internal bleeding
  4. Known bleeding diathesis
  5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR >1.7
  6. Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
  7. Treatment with a thrombolytic within the last 3 months prior to randomization
  8. Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
  9. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
  10. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation
  11. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
  12. For patients with suspected coagulopathy, platelet count must be checked prior to randomization and patient is excluded if baseline platelet count <100,000/mL
  13. Baseline blood glucose >400 mg/dL (22.20 mmol/L)
  14. Baseline blood glucose <50 mg/dL (2.78 mmol/L) needs to be normalized prior to randomization
  15. Clot retrieval attempted using a neurothrombectomy device prior to randomization
  16. Intracranial or intraspinal surgery or trauma within 2 months
  17. Other serious, advanced, or terminal illness with life expectancy less than 6 months (investigator judgment)
  18. History of acute ischemic stroke in the last 90 days
  19. History of hemorrhagic stroke
  20. Presumed septic embolus; suspicion of bacterial endocarditis
  21. 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
  22. Pregnant
  23. Unable to undergo a contrast brain perfusion scan with either MRI or CT
  24. Extensive early ischemic change (hypodensity) on non-contrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax >6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)
  25. Significant mass effect
  26. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
  27. Evidence of intracranial tumor (except small meningioma)