Ischemic Stroke, Stroke, Brain Infarction
Conditions
Keywords
acute ischemic stroke, stroke, rt-PA, thrombolytic, t-PA, recombinant tissue plasminogen activator, Activase, eptifibatide, Integrilin, fibrinolytic agents, clot dissolving, blood clot
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.
Interventions
DRUGEptifibatide
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.
DRUGrt-PA
Intravenous recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Barthel Index ≥ 95 | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Death Due to Stroke Within 7 Days of Treatment Onset | Within 7 days of treatment onset | Death due to stroke within 7 days of treatment onset. Classified by blinded clinical investigators |
| NIH Stroke Scale Score (NIHSS) ≤ 5 | Within 2 hours of treatment onset | Study subjects with an NIH stroke scale score of ≤ 5 at 2 hours from treatment onset, those sedated and unable to be evaluated by the NIHSS were assigned the bad outcome (n=1). The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death. |
| Serious Systemic Bleeding | Within 7 days of treatment onset | Incidence of serious systemic bleeding defined as requiring transfusion of 2 or more units of packed red blood cells. |
| NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days | 90 days from treatment onset | Study subjects with an NIH stroke scale score ≤ 2 points at 90 days from treatment onset compared to baseline value, those dead or unable to be evaluated by the NIHSS were assigned the bad outcome. The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death. |
| NIH Stroke Scale Score (NIHSS) ≤ 2 | Within 24 hours of treatment onset | Study subjects with an NIH stroke scale score of ≤ 2 at 24 hours from treatment onset, those dead (n=1) or sedated and unable to be evaluated by the NIHSS were assigned the bad outcome (n=5). The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death. |
| Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset | Within 7 days of treatment onset | 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 |
| Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset | Within 7 days of treatment onset | Any ICH observed on CT by the study site neuroradiologist and the independent study neuroradiologist; the central reader. The ICH would not be 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,where judgment of significant neurological decline was made by the local clinical investigator. A third independent reader will make the final determination if there is disagreement between the treating investigator and the central reader |
| Death Within 7 Days of Treatment Onset | Within 7 days of treatment onset | Death due to any cause within 7 days of treatment onset |
Countries
United States
Participant flow
Recruitment details
The trial was conducted in emergency departments at 9 US medical centers comprised of 21 hospitals. Subjects were recruited between July 2009 and October 2012.
Pre-assignment details
No enrolled participants were excluded from the trial before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| Rt-PA Only rt-PA (0.9 mg/kg) | 25 |
| Rt-PA and Eptifibatide rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg) | 101 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 20 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Rt-PA Only | Rt-PA and Eptifibatide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 64 Participants | 82 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 37 Participants | 44 Participants |
| Age, Continuous | 70.9 years STANDARD_DEVIATION 13 | 69.0 years STANDARD_DEVIATION 13.6 | 74.2 Years |
| Modified Rankin Score (mRS) 0 | 16 participants | 74 participants | 90 participants |
| Modified Rankin Score (mRS) 1 | 2 participants | 11 participants | 13 participants |
| Modified Rankin Score (mRS) 2 | 3 participants | 7 participants | 10 participants |
| Modified Rankin Score (mRS) 3 | 4 participants | 4 participants | 8 participants |
| Modified Rankin Score (mRS) 4 | 0 participants | 5 participants | 5 participants |
| Modified Rankin Score (mRS) 5 | 0 participants | 0 participants | 0 participants |
| National Institutes of Health Stroke Scale Score (NIHSS) NIHSS <=12 | 10 Participants | 56 Participants | 66 Participants |
| National Institutes of Health Stroke Scale Score (NIHSS) NIHSS >12 | 15 Participants | 45 Participants | 60 Participants |
| National Institutes of Health Stroke Scale Score (NIHSS) | 17 units on a scale | 12 units on a scale | 12 units on a scale |
| Region of Enrollment United States | 25 participants | 101 participants | 126 participants |
| Sex: Female, Male Female | 12 Participants | 48 Participants | 60 Participants |
| Sex: Female, Male Male | 13 Participants | 53 Participants | 66 Participants |
| Stroke symptom onset to intravenous rt-PA start < 1 hour | 0 Participants | 1 Participants | 1 Participants |
| Stroke symptom onset to intravenous rt-PA start 1 to 2 hours | 11 Participants | 56 Participants | 67 Participants |
| Stroke symptom onset to intravenous rt-PA start >2 to 3 hours | 13 Participants | 42 Participants | 55 Participants |
| Stroke symptom onset to intravenous rt-PA start > 3 hours | 1 Participants | 2 Participants | 3 Participants |
| Stroke symptom onset to intravenous rt-PA start | 129 minutes | 113 minutes | 116 minutes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 25 | 80 / 101 |
| serious Total, serious adverse events | 7 / 25 | 26 / 101 |
Outcome results
Primary
Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline
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).
Time frame: 90 days from treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline | mRS of 0-1 or return to baseline | 9 participants |
| Rt-PA Only | Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline | mRS >1 and > baseline | 16 participants |
| Rt-PA and Eptifibatide | Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline | mRS of 0-1 or return to baseline | 50 participants |
| Rt-PA and Eptifibatide | Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline | mRS >1 and > baseline | 51 participants |
p-value: 0.2395% CI: [0.7, 4.31]Regression, Logistic
p-value: 0.5395% CI: [0.51, 3.71]Regression, Logistic
Primary
Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset
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
Time frame: Within 36 hours of initiation of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset | sICH within 36 hours of treatment onset | 3 participants |
| Rt-PA Only | Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset | No sICH within 36 hours of treatment onset | 22 participants |
| Rt-PA and Eptifibatide | Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset | sICH within 36 hours of treatment onset | 2 participants |
| Rt-PA and Eptifibatide | Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset | No sICH within 36 hours of treatment onset | 99 participants |
p-value: 0.05395% CI: [0.01, 1.4]Regression, Logistic
Secondary
Barthel Index ≥ 95
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.
Time frame: 90 days from treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Barthel Index ≥ 95 | Barthel Index ≥ 95 | 11 participants |
| Rt-PA Only | Barthel Index ≥ 95 | Barthel Index < 95 | 14 participants |
| Rt-PA and Eptifibatide | Barthel Index ≥ 95 | Barthel Index ≥ 95 | 55 participants |
| Rt-PA and Eptifibatide | Barthel Index ≥ 95 | Barthel Index < 95 | 46 participants |
p-value: 0.3595% CI: [0.63, 3.67]Regression, Logistic
p-value: 0.8595% CI: [0.4, 3.02]Regression, Logistic
Secondary
Glasgow Outcome Scale (GOS) of 1
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.
Time frame: 90 days from treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Glasgow Outcome Scale (GOS) of 1 | GOS =1 | 10 participants |
| Rt-PA Only | Glasgow Outcome Scale (GOS) of 1 | GOS > 1 | 15 participants |
| Rt-PA and Eptifibatide | Glasgow Outcome Scale (GOS) of 1 | GOS =1 | 52 participants |
| Rt-PA and Eptifibatide | Glasgow Outcome Scale (GOS) of 1 | GOS > 1 | 49 participants |
p-value: 0.395% CI: [0.65, 3.88]Regression, Logistic
p-value: 0.7395% CI: [0.44, 3.24]Regression, Logistic
Other Pre-specified
Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset
Any ICH observed on CT by the study site neuroradiologist and the independent study neuroradiologist; the central reader. The ICH would not be 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,where judgment of significant neurological decline was made by the local clinical investigator. A third independent reader will make the final determination if there is disagreement between the treating investigator and the central reader
Time frame: Within 7 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset | asICH within 7 days of treatment onset | 3 participants |
| Rt-PA Only | Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset | No asICH within 7 days of treatment onset | 22 participants |
| Rt-PA and Eptifibatide | Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset | asICH within 7 days of treatment onset | 16 participants |
| Rt-PA and Eptifibatide | Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset | No asICH within 7 days of treatment onset | 85 participants |
p-value: 0.7695% CI: [0.35, 8.02]Regression, Logistic
Other Pre-specified
Death Due to Stroke Within 7 Days of Treatment Onset
Death due to stroke within 7 days of treatment onset. Classified by blinded clinical investigators
Time frame: Within 7 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Death Due to Stroke Within 7 Days of Treatment Onset | Death due to stroke within 7 days of treatment ons | 3 participants |
| Rt-PA Only | Death Due to Stroke Within 7 Days of Treatment Onset | No Death due to stroke within 7 days of treatment | 22 participants |
| Rt-PA and Eptifibatide | Death Due to Stroke Within 7 Days of Treatment Onset | Death due to stroke within 7 days of treatment ons | 12 participants |
| Rt-PA and Eptifibatide | Death Due to Stroke Within 7 Days of Treatment Onset | No Death due to stroke within 7 days of treatment | 89 participants |
p-value: 0.9999995% CI: [0.24, 5.92]Regression, Logistic
Post Hoc
Death Due to Stroke Within 90 Days of Treatment Onset
Death due to stroke within 90 days of treatment onset. Classified by blinded clinical investigators
Time frame: Within 90 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Death Due to Stroke Within 90 Days of Treatment Onset | Death due to stroke within 90 days of treatment on | 4 participants |
| Rt-PA Only | Death Due to Stroke Within 90 Days of Treatment Onset | No Death due to stroke within 90 days of treatment | 21 participants |
| Rt-PA and Eptifibatide | Death Due to Stroke Within 90 Days of Treatment Onset | No Death due to stroke within 90 days of treatment | 86 participants |
| Rt-PA and Eptifibatide | Death Due to Stroke Within 90 Days of Treatment Onset | Death due to stroke within 90 days of treatment on | 15 participants |
p-value: 0.9999995% CI: [0.26, 4.18]Regression, Logistic
Other Pre-specified
Death Within 7 Days of Treatment Onset
Death due to any cause within 7 days of treatment onset
Time frame: Within 7 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Death Within 7 Days of Treatment Onset | No death within 7 days of treatment onset | 22 participants |
| Rt-PA Only | Death Within 7 Days of Treatment Onset | Death within 7 days of treatment onset | 3 participants |
| Rt-PA and Eptifibatide | Death Within 7 Days of Treatment Onset | Death within 7 days of treatment onset | 12 participants |
| Rt-PA and Eptifibatide | Death Within 7 Days of Treatment Onset | No death within 7 days of treatment onset | 89 participants |
p-value: 0.9999995% CI: [0.24, 5.92]Regression, Logistic
Post Hoc
Death Within 90 Days of Treatment Onset
Death due to any cause within 90 days of treatment onset
Time frame: Within 90 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Death Within 90 Days of Treatment Onset | Death within 90 days of treatment onset | 4 participants |
| Rt-PA Only | Death Within 90 Days of Treatment Onset | No death within 90 days of treatment onset | 21 participants |
| Rt-PA and Eptifibatide | Death Within 90 Days of Treatment Onset | Death within 90 days of treatment onset | 20 participants |
| Rt-PA and Eptifibatide | Death Within 90 Days of Treatment Onset | No death within 90 days of treatment onset | 81 participants |
p-value: 0.7895% CI: [0.38, 5.76]Regression, Logistic
Post Hoc
Modified Rankin Scale (mRS) of 0-1
Modified Rankin Scale of 0 or 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 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).
Time frame: 90 days from treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Modified Rankin Scale (mRS) of 0-1 | mRS of 0-1 | 6 participants |
| Rt-PA Only | Modified Rankin Scale (mRS) of 0-1 | mRS > 1 | 19 participants |
| Rt-PA and Eptifibatide | Modified Rankin Scale (mRS) of 0-1 | mRS of 0-1 | 44 participants |
| Rt-PA and Eptifibatide | Modified Rankin Scale (mRS) of 0-1 | mRS > 1 | 57 participants |
p-value: 0.0795% CI: [0.9, 6.64]Regression, Logistic
p-value: 0.2295% CI: [0.67, 5.88]Regression, Logistic
Other Pre-specified
NIH Stroke Scale Score (NIHSS) ≤ 2
Study subjects with an NIH stroke scale score of ≤ 2 at 24 hours from treatment onset, those dead (n=1) or sedated and unable to be evaluated by the NIHSS were assigned the bad outcome (n=5). The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.
Time frame: Within 24 hours of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤ 2 | NIHSS ≤ 2 | 5 participants |
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤ 2 | NIHSS > 2 | 20 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤ 2 | NIHSS ≤ 2 | 27 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤ 2 | NIHSS > 2 | 74 participants |
p-value: 0.5595% CI: [0.47, 4.07]Regression, Logistic
Other Pre-specified
NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days
Study subjects with an NIH stroke scale score ≤ 2 points at 90 days from treatment onset compared to baseline value, those dead or unable to be evaluated by the NIHSS were assigned the bad outcome. The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.
Time frame: 90 days from treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days | NIHSS ≤ 2 | 11 participants |
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days | NIHSS > 2 | 14 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days | NIHSS ≤ 2 | 45 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days | NIHSS > 2 | 56 participants |
p-value: 0.8295% CI: [0.46, 2.67]Regression, Logistic
Other Pre-specified
NIH Stroke Scale Score (NIHSS) ≤ 5
Study subjects with an NIH stroke scale score of ≤ 5 at 2 hours from treatment onset, those sedated and unable to be evaluated by the NIHSS were assigned the bad outcome (n=1). The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.
Time frame: Within 2 hours of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤ 5 | NIHSS ≤ 5 | 6 participants |
| Rt-PA Only | NIH Stroke Scale Score (NIHSS) ≤ 5 | NIHSS > 5 | 19 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤ 5 | NIHSS ≤ 5 | 35 participants |
| Rt-PA and Eptifibatide | NIH Stroke Scale Score (NIHSS) ≤ 5 | NIHSS > 5 | 66 participants |
p-value: 0.3195% CI: [0.61, 4.99]Regression, Logistic
Other Pre-specified
Serious Systemic Bleeding
Incidence of serious systemic bleeding defined as requiring transfusion of 2 or more units of packed red blood cells.
Time frame: Within 7 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Serious Systemic Bleeding | Serious systemic bleeding | 0 participants |
| Rt-PA Only | Serious Systemic Bleeding | No Serious systemic bleeding | 25 participants |
| Rt-PA and Eptifibatide | Serious Systemic Bleeding | Serious systemic bleeding | 1 participants |
| Rt-PA and Eptifibatide | Serious Systemic Bleeding | No Serious systemic bleeding | 100 participants |
Other Pre-specified
Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset
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
Time frame: Within 7 days of treatment onset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rt-PA Only | Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset | sICH within 7 days of treatment onset | 3 participants |
| Rt-PA Only | Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset | No sICH within 7 days of treatment onset | 22 participants |
| Rt-PA and Eptifibatide | Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset | sICH within 7 days of treatment onset | 2 participants |
| Rt-PA and Eptifibatide | Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset | No sICH within 7 days of treatment onset | 99 participants |
p-value: 0.05395% CI: [0.01, 1.4]Regression, Logistic