The "Combined Approach to Lysis Utilizing Eptifibatide and Rt-PA in Acute Ischemic Stroke-Enhanced Regimen" (CLEAR-ER Stroke Trial)
Overview
- Phase
- Phase 2
- Intervention
- rt-PA
- Conditions
- Ischemic Stroke
- Sponsor
- University of Cincinnati
- Enrollment
- 126
- Locations
- 20
- Primary Endpoint
- Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Arthur Pancioli
Dir Academic Med
University of Cincinnati
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.
Arms & Interventions
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.
Intervention: rt-PA
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.
Intervention: Eptifibatide
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.
Intervention: rt-PA
Outcomes
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(90 days from treatment onset)
- Glasgow Outcome Scale (GOS) of 1(90 days from treatment onset)