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

Condition(s) targeted: Ischemic Stroke; Stroke; Brain Infarction

Intervention: Eptifibatide (Drug); rt-PA (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University of Cincinnati

Official(s) and/or principal investigator(s):
Arthur M Pancioli, MD, Principal Investigator, Affiliation: University of Cincinnati College of Medicine Department of Emergency Medicine
Opeolu M Adeoye, MD, Principal Investigator, Affiliation: University of Cincinnati College of Medicine Department of Emergency Medicine

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.

Official title: The "Combined Approach to Lysis Utilizing Eptifibatide and Rt-PA in Acute Ischemic Stroke-Enhanced Regimen" (CLEAR-ER Stroke Trial)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset

Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline

Secondary outcome:

Barthel Index ≥ 95

Glasgow Outcome Scale (GOS) of 1

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.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

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.

UCLA Ronald Reagan Medical Center, Los Angeles, California 90024, United States

University of California San Diego, San Diego, California 92103, United States

UCLA Medical Center Santa Monica, Santa Monica, California 90404, United States

Washington Hospital Center, Washington, District of Columbia 20010, United States

St. Elizabeth Healthcare Edgewood, Edgewood, Kentucky 41017, United States

St. Elizabeth Healthcare Florence, Florence, Kentucky 41042, United States

St. Elizabeth Healthcare Ft. Thomas, Ft. Thomas, Kentucky 41075, United States

Suburban Hospital, Bethesda, Maryland 20814, United States

University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States

Robert Wood Johnson University Hospital, New Brunswick, New Jersey 08903, United States

Mission Hospital, Inc., Asheville, North Carolina 28801, United States

Bethesda North Hospital, Cincinnati, Ohio 45242, United States

Good Samaritan Hospital, Cincinnati, Ohio 45220-2489, United States

Mercy Hospital Mt Airy, Cincinnati, Ohio 45239, United States

Mercy Hospital, Western Hills, Cincinnati, Ohio 45238, United States

The Christ Hospital, Cincinnati, Ohio 45219, United States

The Jewish Hospital, Cincinnati, Ohio 45236, United States

University Hospital, Cincinnati, Ohio 45219, United States

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

West Virginia University Hospital, Morgantown, West Virginia 26506, United States

CLEAR-ER Stroke Trial web site

Related publications:

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.

Starting date: July 2009
Last updated: March 26, 2014