Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)
Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)
The purpose of this study is to determine which of 3 different doses of tenecteplase (TNK) is
 better for treating stroke patients and if TNK offers an advantage over currently available
 treatment with tissue plasminogen activator (tPA).
Stroke is the third leading cause of death and a leading cause of adult disability in the
 United States and worldwide. To date, the only scientifically-proven and FDA-approved
 treatment for acute stroke is the clot-busting drug, tissue plasminogen activator (tPA). A
 newer clot-busting drug, tenecteplase (TNK), has chemical properties that make it a
 potentially safer and more effective drug for treating stroke. Preliminary testing of TNK in
 patients with acute stroke has been encouraging enough to warrant further testing.

 This study, TNK-S2B, will compare three different doses of TNK with standard tPA treatment in
 patients with acute stroke. Patients will be chosen randomly to receive either TNK or tPA.
 Neither the patient nor his/her doctor will know which medication the patient received until
 the study is completely finished.

 The first part of the study will look at results of treatment in the first 24 hours to select
 the best dose of TNK to carry forward into a more detailed comparison with standard tPA
 treatment. After at least 100-150 pairs of the best dose of TNK and tPA patients have been
 enrolled, entry into the study will pause, and the outcomes at 3 months after stroke will be
 compared to see if the results of TNK treatment are sufficiently promising as an improvement
 over standard treatment to justify expanding the study to find a definitive answer.

 The study, which will be conducted in at least 8 large medical centers, is expected to last
 about 3 years.
Inclusion Criteria:

 -  Patients with at least a serious, measurable deficit on the NIH Stroke Scale in
 language (aphasia score > 1), motor power (arm or leg > 1), vision (best visual score
 > 2), or attention (attention score > 2). Thus eligible patients may have a minimum
 total score of 1 if the deficit is in language or motor power. There is no maximum
 score that is exclusionary; even patients with severe hemispheric or brainstem
 deficits will be eligible, as is current practice with intravenous rt-PA. Patients
 with all ischemic stroke types and in all vascular distributions are eligible.

 -  Must arrive at participating hospital and treatment begun within 3 hours of the onset
 of symptoms. Patients awakening with new symptoms must use the time last observed to
 be normal and awake and the total time cannot exceed three hours prior to treatment as
 the time of onset.

 -  Must be 18 years of age or older.

 Exclusion Criteria:

 -  Patients with a) minor stroke symptoms (e.g., sensory loss, ataxia, dysarthria, or
 facial weakness alone) or b) major symptoms which are rapidly improving by the time of
 treatment.

 -  Patients for whom a complete NIH Stroke Score cannot be obtained (e.g., intubated
 patients or complete amputees).

 -  Patients with evidence of intracranial hemorrhage on pretreatment CT scan.

 -  Patients with a clinical presentation that suggests subarachnoid hemorrhage, even if
 the initial CT scan is normal.

 -  Patients who are known or suspected to be pregnant.

 -  Patients with a known bleeding diathesis or patients with a platelet count < 100,000.
 For patients who are taking oral Warfarin (Coumadin), the results of the pretreatment
 International Normalized Ratio (INR) must be available prior to treatment and must be

 -  </= 1.4. Patients who have received heparin within 48 hours must have a normal partial
 thromboplastin time (PTT) to be eligible. Patients who have received low molecular
 weight heparin or heparinoid within 24 hours are also excluded.

 -  Patients with major surgery or serious trauma excluding head trauma within 14 days or
 serious head trauma within 3 months.

 -  Patients with a history of gastrointestinal or urinary tract hemorrhage in the
 previous 21 days.

 -  Patients with an arterial puncture at a non-compressible site or a lumbar puncture in
 the previous 7 days.

 -  Patients who, on repeated measurement, have a systolic blood pressure > 185, or a
 diastolic blood pressure > 110 mmHg when treatment is to begin, or require aggressive
 treatment to reduce blood pressure to within these limits.

 -  Patients with a history of stroke in the previous 3 months or have ever had an
 intracranial hemorrhage considered to put them at increased risk for intracranial
 hemorrhage.

 -  Patients with a serious medical illness likely to interfere with treatment or
 treatment might adversely affect that illness.

 -  Patients with abnormal blood glucose thought to account for the neurological deficit.

 -  Patients with a clinical presentation consistent with acute myocardial infarction or
 patients with presentation suggesting post-myocardial infarction pericarditis.

 -  Patients with a seizure at onset of stroke thought to be presenting with post-ictal
 paralysis mimicking stroke.

 -  Patients with pre-existing neurological or psychiatric disease that would confound the
 neurological or functional evaluations.

 -  Patients who have received any other investigational drug within 14 days.

 -  Patients who have large areas (greater than one lobe) of obvious low density on the
 baseline CT scan will be presumed to have had ongoing cerebral ischemia for greater
 than 3 hours, and will, therefore, be excluded. Patients with subtle early signs of
 cerebral infarction (e.g., sulcal effacement, blurring of the grey-white junction,
 asymmetry of the basal ganglia, insular ribbon sign, and others) and the dense artery
 sign on baseline CT scan will be eligible. Similarly, evidence of previous remote
 cerebral infarction on baseline CT will not be exclusionary.

 -  Patients for whom informed consent cannot be obtained.