TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion
TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion
This trial will enroll patients that have been diagnosed with a transient ischemic attack
 (TIA) or minor stroke that has occurred within the past 12 hours. Anyone diagnosed with a
 minor stroke faces the possibility of long-term disability and even death, regardless of
 treatment. Stroke symptoms such as weakness, difficulty speaking and paralysis may improve or
 worsen over the hours or days immediately following a stroke. The purpose of this research
 trial is to study the effects of a clot-dissolving drug, tenecteplase (TNK-tPA), as a
 treatment for patients who arrive within twelve hours from stroke onset. This study is
 attempting to see if TNK-tPA given through a vein in the arm (intravenous) to patients is a
 safe treatment for stroke patients. Neither the safety nor the effectiveness of this
 treatment has been proven yet.

 This trial will be conducted at several site in Canada.

 Dr Michael Hill and Dr. Shelagh Coutts are the Principal Investigators of this trial,
 coordinated at the University of Calgary, Foothills Medical Centre.
The primary objective of TEMPO-1 is to demonstrate the safety and feasibility of using
 TNK-tPA (tenecteplase), a thrombolytic agent that is relatively novel to the treatment
 ischemic stroke but well-established in the treatment of myocardial infarction, to treat
 minor ischemic stroke patients with proven acute symptomatic occlusions. Up to 80% of
 ischemic stroke is minor and initially non-disabling. These patients present with a transient
 ischemic attack (TIA) or minor stroke.An overwhelming majority are not treated with
 thrombolysis as they are considered "too good to treat" by most physicians.

 TEMPO-1 will enroll patients within a 12 hour time window with a NIHSS score of <6 and an
 ASPECTS >5. Patients must have an intracranial occlusion on CTA. Study drug must be
 administered within 90 minutes from the first slice of CTA. This is an open- label,
 multi-centre trial, dose- escalated trial. A total of 50 patients will be enrolled, 25 per
 tier. There will two dose tiers at 0.1 mg/kg and 0.25 mg/kg. Advancement to the second
 dose-tier will be dependent upon safe completion of the 1st dose tier and the approval of the
 DSMB.

 Patients will undergo a study CT angiogram of the intracranial circulation between 4-8 hours
 after treatment to determine the biological effect of the drug - whether the occluded artery
 has recanalized or not. Patients will be assessed at 24 and 48 hours, and at Days 5, 30, and
 90.
Inclusion Criteria:

 1. Acute ischemic stroke in an adult patient (18 years of age or older)

 2. Onset (last-seen-well) time to treatment time < 12 hours.

 3. Minor stroke defined as a baseline NIHSS < 6 at the time of randomization. Patients
 must have a demonstrable neurological deficit on physical neurological examination.

 4. Any acute intracranial occlusion (MCA, ACA, PCA, VB territories) defined by
 non-invasive acute imaging (CT angiography) that is neurologically relevant to the
 presenting symptoms and signs. An acute occlusion is defined as TICI 0 or TICI 1 flow.

 5. Pre-stroke independent functional status in activities of daily living with pre-stroke
 estimated modified Barthel Index of 90 or greater AND premorbid mRS 0 or 1.

 6. Informed consent from the patient or surrogate.

 7. Patients can be treated within 90 minutes of the CT/CTA being completed.

 Exclusion Criteria:

 1. Hyperdensity on NCCT consistent with any intracranial hemorrhage. Any clinical
 suspicion of any intracranial hemorrhage even in the absence of visible blood on
 baseline brain imaging.

 2. Large acute stroke >1/3 MCA territory or ASPECTS<5 visible on baseline CT scan.

 3. Core of established infarction. No area of grey matter hypodensity at a similar or
 lesser density to white matter or in the judgment of the enrolling neurologist is
 consistent with a subacute ischemic stroke > 12 hours of age.

 4. Clinical history, past imaging and clinical judgment suggest that the intracranial
 occlusion is chronic.

 5. Patient is a candidate for and should receive standard of care IV tPA.

 6. Stroke occurring as an in-patient. An in-patient is a person who has been officially
 admitted to the hospital to a ward bed. A patient in the ED who has not been formally
 admitted is still considered to be an outpatient.

 7. Patient has a severe or fatal or disabling illness that will prevent improvement or
 follow-up or such that the treatment would not likely benefit the patient.

 8. Patient cannot complete follow-up due to co-morbid non-fatal illness or is visiting
 the host sites city and cannot return for follow-up.

 9. Pregnancy.

 10. Patient is actively taking dual antiplatelet medication (aspirin & clopidogrel) in the
 last 48 hours.

 11. International normalized ratio > 1.4

 12. Standard thrombolysis exclusions (Taken from Canadian guidelines1)

 NOTES: NIHSS = National Institutes of Health Stroke Scale ACA = anterior cerebral artery
 MCA = middle cerebral artery ICA = internal cerebral artery PCA = posterior cerebral artery
 VB = vertebrobasilar TICI = thrombolysis in cerebral ischemic scale CT = computed
 tomography NCCT = non-contrast CT CTA = CT angiography ASPECTS = Alberta Stroke Program
 Early CT Score IV = intravenous tPA = tissue plasminogen activator ED = Emergency
 Department