Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR Stroke) Trial

Stroke Clinical Trial

Official title:

Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR Stroke) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00250991
• Other study ID #: P50NS044283
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 7, 2005
• Last updated: May 7, 2009
• Start date: July 2003
• Est. completion date: July 2007

Study information

• Verified date: May 2009
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is determine the effects of using of a combination of two drugs--integrilin (eptifibatide) and activase (recombinant tissue plasminogen activator, rt-PA, or recombinant t-PA)--to dissolve blood clots in patients who have a stroke.

Description:

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR Stroke) trial is 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.

The CLEAR Stroke study will enroll 100 participants with acute stroke due to a blood clot. The purpose of this multi-center, randomized, double-blind study is to determine the effects of using a combination of two drugs, integrilin (or eptifibatide) and activase (or recombinant tissue plasminogen activator, rt-PA, recombinant t-PA), to dissolve blood clots. More specifically, the CLEAR study is being done to determine if a lower dose of activase, given in combination with a second drug, integrilin, is a safe treatment for acute stroke.

Activase, 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. Integrilin is also already FDA-approved as a treatment for blood clots causing heart attack. The investigational aspect of this study is the use of integrilin for a stroke victim in combination with activase.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 that intravenous study drug is begun.

• Age: 18 through 80 years (i.e. candidates must have had their 18th birthday, but not had their 81st birthday).

• Intravenous 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 prothrombin time greater than 15 or INR > 1.4

• 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

• If heparin has been administered within 48 hours, the patient must have a normal partial thromboplastin time (PTT)

• 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.

Exclusion Criteria/CT Scan:

• 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.

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• activase

• integrilin

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital, 1200 South Cedar Crest Blvd	Allentown	Pennsylvania
United States	University of Michigan, University of Michigan Health System, 1500 E. Medical Center Drive, TC B1354, Box 0303	Ann Arbor	Michigan
United States	Good Samaritan Hospital, 375 Dixmyth Ave.,	Cincinnati	Ohio
United States	Mercy Hospital, Mt Airy, 2446 Kipling Ave.	Cincinnati	Ohio
United States	Mercy Hospital, Western Hills, 3131 Queen City Ave.	Cincinnati	Ohio
United States	The Christ Hospital, 2139 Auburn Ave.	Cincinnati	Ohio
United States	The Jewish Hospital of Cincinnati, 4777 East Galbraith Rd,	Cincinnati	Ohio
United States	University of Cincinnati, University Hospital, 234 Goodman Ave.	Cincinnati	Ohio
United States	St. Elizabeth Medical Center South, One Medical Village Drive	Edgewood	Kentucky
United States	University of California, Los Angeles, UCLA Medical Center, 10833 Le Conte Ave.	Los Angeles	California
United States	Jewish Hospital Louisville, Jewish Hospital Healthcare Services Inc., 200 Abraham Flexner Way	Louisville	Kentucky
United States	Bethesda North Hospital, 10500 Montgomery Rd	Montgomery	Ohio
United States	Vanderbilt University, University Hospital, 1211 22nd Ave. S.	Nashville	Tennessee
United States	Long Island Jewish, North Shore-Long Island Jewish Health System, 270-05 76 Avenue	New Hyde Park	New York
United States	University of Pennsylvania, University of Pennsylvania Medical Center, 3400 Spruce Street	Philadelphia	Pennsylvania
United States	Barrow Neurologic Institute, St. Joseph's Hospital and Medical Center, 350 West Thomas Rd	Phoenix	Arizona
United States	Brown University, Rhode Island Hospital, 593 Eddy St.	Providence	Rhode Island
United States	Santa Monica-UCLA Medical Center, 1250 16th Street	Santa Monica	California
United States	St. John's Health Center, 1328 22nd St	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary safety endpoint in this safety study will be the incidence of symptomatic intracranial hemorrhage .		within 36 hours	Yes
Primary	The primary measure of early beneficial drug activity will be the incidence of early neurological improvement, as measured by the NIHSSS </= 2		at 24 hours from symptom onset	Yes