Clinical trial NCT00894803: Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke
Official title: The "Combined Approach to Lysis Utilizing Eptifibatide and Rt-PA in Acute Ischemic Stroke-Enhanced Regimen" (CLEAR-ER Stroke Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke
Stroke
Brain Infarction
Keywords: acute ischemic stroke
stroke
rt-PA, thrombolytic
t-PA
recombinant tissue plasminogen activator
Activase
eptifibatide
Integrilin
fibrinolytic agents
clot dissolving
blood clot
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2009-05-07
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset
timeFrame: Within 36 hours of initiation of therapy
measure: Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline
timeFrame: 90 days from treatment onset
Secondary outcomes:
measure: Barthel Index ≥ 95
timeFrame: 90 days from treatment onset
measure: Glasgow Outcome Scale (GOS) of 1
timeFrame: 90 days from treatment onset
Other outcomes:
measure: Serious Systemic Bleeding
timeFrame: Within 7 days of treatment onset
measure: Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset
timeFrame: Within 7 days of treatment onset
measure: Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset
timeFrame: Within 7 days of treatment onset
measure: Death Within 7 Days of Treatment Onset
timeFrame: Within 7 days of treatment onset
measure: Death Due to Stroke Within 7 Days of Treatment Onset
timeFrame: Within 7 days of treatment onset
measure: NIH Stroke Scale Score (NIHSS) ≤ 5
timeFrame: Within 2 hours of treatment onset
measure: NIH Stroke Scale Score (NIHSS) ≤ 2
timeFrame: Within 24 hours of treatment onset
measure: NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days
timeFrame: 90 days from treatment onset
Locations:
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center Santa Monica
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare Edgewood
state: Kentucky
city: Florence
country: United States
facility: St. Elizabeth Healthcare Florence
state: Kentucky
city: Ft. Thomas
country: United States
facility: St. Elizabeth Healthcare Ft. Thomas
state: Kentucky
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Asheville
country: United States
facility: Mission Hospital, Inc.
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: The Jewish Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Mercy Hospital, Western Hills
state: Ohio
city: Cincinnati
country: United States
facility: Mercy Hospital Mt Airy
state: Ohio
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
Study officials:
affiliation: University of Cincinnati College of Medicine Department of Emergency Medicine
name: Arthur M Pancioli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati College of Medicine Department of Emergency Medicine
name: Opeolu M Adeoye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.