TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion "TEMPO-1"

Completed

Phase 2 Results N/A

Update History

22 Nov '14
A location was updated in Calgary.
New
The overall status was removed for University of Calgary.
22 Feb '13
The description was updated.
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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.
Old
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 1 hour 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.
The eligibility criteria were updated.
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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)
Old
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 60 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 white matter hypodensity at a similar or lesser density to grey 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 (such as psychiatric 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 guidelines)