Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR)
Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR)
The primary goal of this trial is to determine if individuals with acute ischemic stroke
 treated with a full dose of IV recombinant tissue plasminogen activator (rt-PA) plus IV
 eptifibatide started within 3 hours of symptom onset are more likely to have a better outcome
 than individuals treated with standard IV rt-PA alone.
The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Full
 Dose Regimen (CLEAR-FDR Stroke Trial) is a Phase II trial and part of the Specialized Program
 on Translational Research in Acute Stroke (SPOTRIAS). The overall goals of SPOTRIAS are to
 enhance delivery of acute stroke patient care and train acute stroke translational
 researchers.

 Stroke most often occurs when blood flow to the brain stops because it is blocked by a blood
 clot. When a blood clot blocks the blood supply to the brain, parts of the brain may not get
 enough blood and oxygen to survive. As a result, permanent brain damage can occur, which can
 affect a person's ability to walk, talk, and function independently. In order to reduce the
 risk of permanent damage, it is important to restore blood flow to the brain as quickly as
 possible.

 rt-PA, used alone, is already approved by the Food and Drug Administration (FDA) as treatment
 for patients with a stroke caused by blockage of an artery in the brain and when given within
 3 hours of the onset of stroke symptoms. Eptifibatide is also already FDA-approved as a
 treatment for blood clots causing heart attack. The investigational aspect of this study is
 the use of eptifibatide for a stroke victim in combination with rt-PA.

 The CLEAR Stroke Trial demonstrated that the combination of low dose rt-PA plus eptifibatide
 can be safely given to acute ischemic stroke patients within 3 hours of symptom onset.

 The CLEAR-ER Stroke Trial demonstrated that the combination of medium dose rt-PA plus
 eptifibatide can be safely given to acute ischemic stroke patients within 3 hours of symptom
 onset.

 The CLEAR-FDR Stroke Trial is designed to provide data concerning the risks when combining
 eptifibatide with full dose intravenous rt-PA in 30 acute ischemic stroke patients within 3
 hours of symptom onset.
Inclusion Criteria:

 -  Patients must have a serious measurable neurological deficit on the NIH Stroke Scale
 due to focal brain ischemia.

 -  An NIH Stroke Scale score >5 at the time the rt-PA is begun.

 -  Age: 18 through 85 years (i.e. candidates must have had their 18th birthday, but not
 had their 86th birthday).

 -  Intravenous rt-PA therapy must be initiated within 3 hours of onset of stroke
 symptoms.

 Exclusion Criteria:

 -  History of stroke in the past 3 months.

 -  Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial
 venous malformation.

 -  Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is
 normal.

 -  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.

 -  Presumed septic embolus.

 -  Presumed pericarditis including pericarditis after acute myocardial infarction.

 -  Recent (within 30 days) surgery or biopsy of parenchymal organ.

 -  Recent (within 30 days) trauma, with internal injuries or ulcerative wounds.

 -  Recent (within 90 days) severe head trauma or head trauma with loss of consciousness.

 -  Any active or recent (within 30 days) serious systemic hemorrhage.

 -  Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or
 oral anticoagulant therapy with International Normalized Ratio (INR) > 1.7.

 -  Baseline lab values: positive urine pregnancy test, glucose < 50 or > 400 mg/dl,
 platelets <100,000 /mm3, Hct <25 %, or creatinine > 4 mg/dl.

 -  Ongoing renal dialysis, regardless of creatinine.

 -  Subjects who received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin,
 Tinzaparin) as deep vein thrombosis (DVT) prophylaxis or in full dose within the
 previous 24 hours.

 -  Subjects who received heparin or a direct thrombin inhibitor (such as bivalirudin,
 argatroban, or lepirudin) within 48 hours from screening must have had a normal
 partial prothrombin time (PTT).

 -  Subjects who received Factor Xa inhibitors (such as fondaparinux) or direct thrombin
 inhibitors (such as dabigatran) within the last 4 days.

 -  Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7
 days.

 -  Seizure at onset of stroke.

 -  Pre-existing neurological or psychiatric disease that would confound the neurological
 or functional evaluations.

 -  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.

 -  Patients whose peripheral venous access is so poor that they are unable to have two
 standard peripheral intravenous lines started.

 -  Current participation in another research drug treatment protocol. Patient cannot
 start another experimental agent until after 90 days.

 -  Informed consent is not or cannot be obtained.

 -  Any known history of amyloid angiopathy.

 -  High density lesion consistent with hemorrhage of any degree.

 -  Significant mass effect with midline shift.

 -  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.