Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke

NCT ID: NCT00894803

Last Updated: 2014-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2012-12-31

Brief Summary

The primary goal of this trial is to determine if individuals with acute ischemic stroke treated with a medium dose of IV 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.

Detailed Description

The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA (recombinant tissue plasminogen activator) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER 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 (NCT00250991) 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 is designed to provide data concerning the risks and benefits of combining eptifibatide with medium dose intravenous rt-PA in 126 acute ischemic stroke patients within 3 hours of symptom onset. Patients will be randomized to a combined intravenous medium-dose rt-PA and eptifibatide regimen, or standard dose rt-PA in a 5 to 1 ratio. This will result in a total of 105 patients treated with a combined regimen, and 21 patients treated with standard dose IV rt-PA alone.

Conditions

Ischemic Stroke; Stroke; Brain Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

rt-PA only

Subject will receive the standard dose (0.9mg/kg) of IV rt-PA given over 60 minutes. One out of 6 subjects will be in this group.

Group Type: ACTIVE_COMPARATOR

rt-PA

Intervention Type: DRUG

Intravenous recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy.

rt-PA and Eptifibatide

Subject will receive the standard dose (0.9mg/kg) of IV rt-PA. This IV dose will be discontinued at 40 minutes. The subject will immediately receive an IV bolus of 135mcg/kg eptifibatide followed by an IV infusion of 0.75 mcg/kg/min eptifibatide for 2 hours. Five out of six subjects will be in this group.

Group Type: EXPERIMENTAL

Eptifibatide

Intervention Type: DRUG

IV Eptifibatide is an approved drug by the Food and Drug Administration as a treatment for blood clots causing heart attack and chest pain.Eptifibatide inhibits platelet aggregation by blocking activated platelets from binding fibrinogen.

rt-PA

Intervention Type: DRUG

Intravenous recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy.

Interventions

Eptifibatide

IV Eptifibatide is an approved drug by the Food and Drug Administration as a treatment for blood clots causing heart attack and chest pain.Eptifibatide inhibits platelet aggregation by blocking activated platelets from binding fibrinogen.

Intervention Type: DRUG

rt-PA

Intravenous recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy.

Intervention Type: DRUG

Other Intervention Names

Integrilin; Activase

Eligibility Criteria

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 Iinternational Normalized Ratio (INR) > 1.7.
• Baseline lab values: positive urine pregnancy test, glucose < 50 or > 400 mg/dl, platelets <100,000 /mm3, Hct (hematocrit) <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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Arthur Pancioli

Dir Academic Med

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arthur M Pancioli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati College of Medicine Department of Emergency Medicine

Opeolu M Adeoye, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati College of Medicine Department of Emergency Medicine

Locations

UCLA Ronald Reagan Medical Center

Los Angeles, California, United States

University of California San Diego

San Diego, California, United States

UCLA Medical Center Santa Monica

Santa Monica, California, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

St. Elizabeth Healthcare Edgewood

Edgewood, Kentucky, United States

St. Elizabeth Healthcare Florence

Florence, Kentucky, United States

St. Elizabeth Healthcare Ft. Thomas

Fort Thomas, Kentucky, United States

Suburban Hospital

Bethesda, Maryland, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Mission Hospital, Inc.

Asheville, North Carolina, United States

The Christ Hospital

Cincinnati, Ohio, United States

University Hospital

Cincinnati, Ohio, United States

Good Samaritan Hospital

Cincinnati, Ohio, United States

The Jewish Hospital

Cincinnati, Ohio, United States

Mercy Hospital, Western Hills

Cincinnati, Ohio, United States

Mercy Hospital Mt Airy

Cincinnati, Ohio, United States

Bethesda North Hospital

Cincinnati, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Countries

United States

References

Barreto AD, Pedroza C, Grotta JC. Adjunctive medical therapies for acute stroke thrombolysis: is there a CLEAR-ER choice? Stroke. 2013 Sep;44(9):2377-9. doi: 10.1161/STROKEAHA.113.001830. Epub 2013 Jul 25. No abstract available.

Reference Type: BACKGROUND

PMID: 23887845 (View on PubMed)

Pancioli AM, Adeoye O, Schmit PA, Khoury J, Levine SR, Tomsick TA, Sucharew H, Brooks CE, Crocco TJ, Gutmann L, Hemmen TM, Kasner SE, Kleindorfer D, Knight WA, Martini S, McKinney JS, Meurer WJ, Meyer BC, Schneider A, Scott PA, Starkman S, Warach S, Broderick JP; CLEAR-ER Investigators. Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke. 2013 Sep;44(9):2381-7. doi: 10.1161/STROKEAHA.113.001059. Epub 2013 Jul 25.

Reference Type: RESULT

PMID: 23887841 (View on PubMed)

Other Identifiers

00894803

Identifier Type: REGISTRY

Identifier Source: secondary_id

P50NS04483-06

Identifier Type: -

Identifier Source: org_study_id