Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN)

Study Overview
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Brief Summary
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This is a double-blind parallel arm randomized trial aimed to assess efficacy and safety of intravenous Tenecteplase compared to intravenous Alteplase in eligible patients who present with symptoms of acute ischemic stroke within 3 to 4.5 hours from onset.

Detailed Description
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Patients presenting with symptoms of acute ischemic stroke (AIS) who present within 3 to 4.5 hours of symptom onset and who meet the inclusion criteria for intravenous (IV) thrombolysis will receive, in a randomized, double-blind fashion, either IV Alteplase at 0.9 mg/kg per standard protocol or IV Tenecteplase at 0.25 mg/kg with saline infusion over one hour. Patients must also have no exclusion criteria for IV thrombolysis within the 3 to 4.5 hour window. The only required imaging is non-contrasted CT of the head. Patients will be monitored according to standard post-thrombolytic care. A CT of the head will be performed at 24 hours based on standard protocol or if there is any neurological change. Neurological function at 24 hours using NIHSS and at 3 months based on modified mRS and the NIHSS.

Official Title
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Phase IIb Study Comparing Tenecteplase to Alteplase in Acute Ischemic Stroke Within 3 to 4.5 Hours From Symptom Onset

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Tenecteplase
* Drug: Alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 80 years Acute neurologic deficit with an NIHSS ≥ 4 Non-enhanced computed tomography (NECT) of the head showing no hemorrhage Acute ischemic stroke symptoms with onset, or time last known well, clearly defined between 3 and 4.5 hours Treatment can be initiated within 3 to 4.5 hours from symptom onset Exclusion Criteria: Evidence of intracranial hemorrhage on NECT Clinical suspicion of subarachnoid hemorrhage even with normal NECT NECT shows hypo-density greater than 1/3 cerebral hemisphere) History of intracranial hemorrhage/stroke Uncontrolled HTN: At time treatment begins SBP remains >185 mmHg or DBP remains >110 mmHg despite repeated measurements Known arteriovenous malformation, neoplasm, or aneurysm Witnessed seizure at stroke onset Acute bleeding tendencies Platelet count <100,000/mm3 Heparin received in prior 48 hours with elevated aPTT Current use of an anticoagulant (Coumadin/Warfarin) irrespective of INR Prior use (within 48 hours) of direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban) Within prior 3 months: intracranial or spinal surgery, head trauma, or previous stroke Arterial puncture at non-compressible site within last 7 days Woman of child bearing age who has a positive pregnancy test NIH stroke scale >25 (severe deficit) or <4 and no dysphasia (mild deficit) or rapidly improving Symptoms spontaneously clearing 14 days post-operative or post major trauma Recent gastrointestinal or urinary tract hemorrhage within the past 21 days Recent acute MI within the past 3 months Serum glucose <50 mg/dl or >400 mg/dL Age >80 or less than 18 History of ischemic stroke AND diabetes mellitus Unable to obtain consent from patient or power of attorney Baseline mRS > 2 Consent not obtained by 20 minutes prior to closure of the therapeutic window. The subject has been treated with a thrombolytic agent within the past 72 hours The subject is a pregnant woman (positive serum βHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy) The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenecteplase<br>Tenecteplase 0.25 mg/kg IV - Maximum dose: 25 mg | Drug: Tenecteplase<br>* Tenecteplase 0.25 mg/kg IV - Maximum 25 mg<br>* Other names: TNKase;|
| Active Comparator: Alteplase<br>Alteplase 0.9 mg/kg IV - Maximum dose: 90 mg | Drug: Alteplase<br>* Alteplase 0.9 mg/kg IV - Maximum: 90 mg<br>* Other names: t-PA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological outcome | Measured by modified Rankin Scale score | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic intracranial hemorrhage | Twenty-four hour brain CT scan showing intracranial hemorrhage in conjuction with neurological deterioration of 4 points or more on the NIHSS | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Infarction, Ischemic Stroke, Thrombolysis