Current partner codePEPTIDESDE
NCT00894803·Phase 2·INTERVENTIONAL

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

Status

Completed

Phase

Phase 2

Enrollment

126

Locations

20

Results

Posted

Publications

2

Study summary

What the protocol is testing.

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.

Full 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.

Interventions

Treatment arms and agents.

DRUG

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.

DRUG

rt-PA

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

Timeline

From registration to results.

  1. First posted

    May 7, 2009

  2. Study start

    Jul 2009

  3. Primary completion

    Oct 2012

  4. Study completion

    Dec 2012

  5. Results posted

    Mar 17, 2014

  6. Registry updated

    Apr 17, 2014

Outcomes

What the study measures.

Primary outcomes

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

Time frame · Within 36 hours of initiation of therapy

Primary safety outcome measure - Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator

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

Time frame · 90 days from treatment onset

Primary efficacy outcome measure - Modified Rankin Scale of 0 or 1 or return to the pre-stroke value at baseline or better. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days were given a value of '6', and assigned the "bad" outcome. Also those lost to follow-up were assigned the "bad" outcome. The Modified Rankin Score (mRS) is a 6 point ordinal scale, measuring functional status. 0 (no symptoms at all), 5 (severe disability; bedridden, incontinent, and requiring constant nursing care).

Secondary outcomes

Barthel Index ≥ 95

Time frame · 90 days from treatment onset

Barthel index score of ≥ 95. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days and those lost to follow-up were assigned the "bad" outcome. The Barthel index is a score comprised of 10 individual items. Each item may be scored 0, 5, 10 or 15; not all items use the full range of 4 possible values. The individual items are summed to produce a total score between 0 and 100; where 0 is inferior performance and 100 is optimal. A score of ≥ 95 is usually considered excellent.

Glasgow Outcome Scale (GOS) of 1

Time frame · 90 days from treatment onset

Glasgow outcome scale score of 1 versus greater than 1. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days and those lost to follow-up were assigned the "bad" outcome. The Glasgow Outcome Scale is scored; 1=good recovery, 2=moderately disabled, 3=severely disabled, 4=vegetative survival, 5=dead.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
85 Years
Sex
ALL
Healthy volunteers
No

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.

Study locations

20 registered sites.

United States. Showing up to 24 locations stored in the fast local snapshot.

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

Related trials

More studies on Eptifibatide.

Related PeptideStat pages

Put the record in context.

Research pages describe evidence. Vendor pages, where available, describe independently tracked research-product listings and are not clinical recommendations.