Principal Investigator:
P.I.: Phillip A. Scott, MD

Study Abstract (brief description, 3 - 5 sentences), including "short name of the study":
The CLEAR trail is a study evaluating the safety of a combination of eptifibatide (Integrillin) and low dose rt-PA (Activase) compared to standard dose rt-PA (Activase) for acute ischemic stroke. This is a multicenter, randomized, double-blinded, placebo controlled trail sponsored by the NIH. Patients are being followed for multiple safety and efficacy parameters for 3 months following their stroke. Study drug is started in the ED within 3 hours of stroke onset and all infusions will be completed within 2 hours of the start time. Some of the patients enrolled in this study will receive study drug under 2 hours from symptoms onset, and some patients in the study will receive study drug between 2 and 3 hours from symptom onset.

IRB# and approval date:
2003-0023 02/06/2003

Study Start and End Dates:
Start Date: June 2003 and End Date: June 2008 (expected 5 years)

Inclusion criteria:

1. Patients must have a serious neurological deficit on the NIH Stroke Scale due to focal brain ischemia
2. NIH Stroke Scale score > 5 at the time that intravenous study drug is begun
3. Age: 18 through 80 years (patients must be 18 years old but have not had their 81st birthday)
4. Intravenous therapy must be initiated within 3 hours of stroke symptom onset
5. At each center, there must not be more than 5 patients enrolled at > 120 minutes from symptom onset for every 2 patient enrolled is less than or equal to 120 minutes

Exclusion criteria:

1. History of stroke in the past 3 months
2. Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
3. Clinical presentation suggesting a subarachnoid hemorrhage, even if initial CT scan is normal
4. Hypertension at time of treatment; systolic BP>185 or diastolic>110 mmHg or aggressive measures to lower blood pressure to below these limits are needed.
5. Presumed septic embolus
6. Presumed pericarditis including pericarditis after acute myocardial infarction
7. Recent (within 30 days) surgery or biopsy of parenchymal organ
8. Recent (within 30 days) trauma, with internal injuries or ulcerative wounds
9. Recent (within 90 days) severe head trauma or head trauma with loss of consciousness
10. Any active or recent (within 30 days) serious systemic hemorrhage
11. Known hereditary or acquired hemorrhagic diathesis, coagulation facot deficiency; or oral anticoagulant therapy with prothrombin time greater than 15 or INR > 1.4
12. Baseline lab values: positive urine pregnancy test, glucose <50 or> 400 mg/dl, platelets< 100,000/mm3, Hct<25%, or creatinine >4mg/dl
13. Ongoing renal dialysis, regardless of creatine
14. If heparin has been administered within 48 hours, the patient must have a normal partial thromboplastin time (PTT)
15. Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days
16. Seizure at onset of stroke
17. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
18. Other serious, advanced, or terminal illness or any other condition that the investigator feels would pose a significant hazard to the patient if rt-PA or eptifibatide therapy were initiated
19. Patients whose peripheral venous access is so poor that they are unable to have two standard peripheral intravenous lines started
20. Current participation in another research drug treatment protocol. Patient cannot start another experimental agent until after 90 days
21. Informed consent is not or cannot be obtained
22. Any known history of amyloid angiopathy

CT Scan Exclusions

1. High density lesion consistent with hemorrhage of any degree
2. Significant mass effect with midline shift
3. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment.

Names of staff working on study, including beeper and telephone number:
Upon initial patient presentation for enrollment into this trial, please page the Brain Injury Group, pager 90004, and someone will return your call.

Investigators
Philip scott, MD Department of Emergency Medicine, pager 3495
Susan Hickenbottom, MD Department of Neurology, pager 3772
William Barsan, MD Department of Emergency Medicine, pager 3373
Robert Silbergleit, MD Department of Emergency medicin, pager 10703
Lewis Morgenstern, MD Department of Neurology, pager 13816
Jeffrey Kutcher, MD Department of Neurology, pager 12361
Rodney Smith, MD Department of Emergency Medicine, SJMH, pager 670-6080

Clinical Coordinators
Jason Schwartz, RN Department of Emergency Medicine UofM, pager 31119
Shirley Frederiksen, RN Department of Emergency Medicine SJMH, pager 670-7977

Will any test be charges to the study? If yes, please list and provide billing information.
Tests that will be charged to the study include the following:

Baseline test - urine pregnancy test, type and screen, proteonomic study labs
Tests at 2 hour interval - proteonomic study labs
Tests at 24 hour +/- 6 hours interval - CT scan, MRI/MRA scan, proteonomic study labs

Special account established thru hospital finance; these tests will be charges directly to the research account.

Is the subject having tests and procedures done that will be relevant to their care in the ED or follow-up from the ED? If yes, what are the tests/procedures? Who will be responsible for interpreting those results and reporting them to the patient and , if appropriate, providing recommendations for follow-up?
Pertinent tests completed in the Emergency Department include:

1. Initial CT scan
2. Baseline labs - CBC w/platelets, Electrolytes, PT/PTT, Type and Screen, Urine pregnancy test

The study investigator and/or the Emergency Department physician caring for the patient will be responsible for interpreting the result of all tests in the ED and will be responsible for reporting them to the patient. The initial head CT will be interpreted by the investigator with the aid of the attending radiologist. If a patient is enrolled into a study, the study investigator and the study coordinator will work collaboratively in assuring that proper follow up is completed as part of the clinical trail. If a patient is not enrolled in the study, the emergency department caring physician will be responsible for providing recommendations for follow-up.