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).

Condition	Intervention	Phase
Stroke	Drug: tenecteplase  Drug: tissue plasminogen activator, tPA	Phase II

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcomes: Functional Handicap (Modified Rankin Score) at 3 months.
Secondary Outcomes: Major Neurological Improvement at 24 hours; Activities of Daily Living at 3 months; Neurological Deficits at 3 months; Functional/Cognitive Outcome at 3 months; Safety
Expected Total Enrollment:  600

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00252239

Martha Davis, R.N.      434-243-6319 
Rachel Arbing, B.S., M.S.      212-342-1259 

California
      University of California at San Diego, San Diego,  California,  92103-8466,  United States
Maryland
      Johns Hopkins-Bayview Medical Center, Baltimore,  Maryland,  21224,  United States
Michigan
      University of Michigan, Ann Arbor,  Michigan,  48109-0316,  United States
New York
      Long Island Jewish Hospital, New Hyde Park,  New York,  11040,  United States
      Columbia University, Statistical Analysis Center, New York,  New York,  10032,  United States
Texas
      University of Texas at Houston, Houston,  Texas,  77030,  United States
Virginia
      University of Virginia Health System, Charlottesville,  Virginia,  22908,  United States

Study chairs or principal investigators

E. Clarke Haley, Jr., M.D.,  Principal Investigator,  Clinical Coordinating Center, Department of Neurology, University of Virginia Health System   
John L. P. Thompson, Ph.D.,  Principal Investigator,  Statistical Analysis Center, Department of Biostatistics, Mailman School of Public Health   

Study ID Numbers:  R01NS37666; R01NS45170; CRC
Last Updated:  December 8, 2005
Record first received:  November 10, 2005
ClinicalTrials.gov Identifier:  NCT00252239
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10