PRISMS

Principal Investigator: Jana Wold
Keywords: Acute Stroke Department: Neurology
IRB Number: 00072831 Co Investigator: Dana DeWitt
Specialty: Neurology, Neurology
Sub Specialties: Neuro Critical Care, Stroke
Recruitment Status: Terminated

Contact Information

Crystal Neate
crystal.neate@hsc.utah.edu
801.583.1018

Brief Summary

Primary Objectives
The primary objective of this study is to determine the efficacy of intravenous (IV) alteplase for treatment of acute ischemic stroke (AIS) in patients with mild stroke (also known as “minor neurologic deficit” and “rapidly improving stroke symptoms”), defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 and not clearly disabling, within 3 hours of last known well time as measured by the proportion of patients with a modified Rankin Scale (mRS) score of 0−1 at Day 90.
Secondary Objectives
The secondary objectives of this study are as follows:
• To further evaluate efficacy of IV alteplase to improve mild stroke outcomes at Day 90 via:
- Ordinal mRS
- Global favorable recovery (Global Outcome Measure derived from mRS 0 − 1, NIHSS 0 − 1, Barthel Index [BI] ≥ 95, and Glasgow Outcome Scale [GOS] =1)
• To evaluate safety as measured by:
- Symptomatic intracranial hemorrhage (sICH) within 36 hours − primary safety assessment
- Any intracranial hemorrhage (ICH) within 36 hours
- Mortality within 90 days
- Stroke-related and neurological deaths within 90 days
- Incidence, severity, and spectrum of all adverse events (AEs) and serious adverse events (SAEs)
Exploratory Objectives
The exploratory objectives for this study include subgroup analyses of the primary efficacy outcome variable in subgroups defined by age (< 65 vs. ≥ 65), pre-treatment NIHSS score (0 − 2 vs. 3 − 5), last known well time to treatment (0 − 2 hours vs. >2− 3 hours), and stroke subgroups (rapidly improving stroke symptoms [RISS] vs. non-RISS), respectively.
The following endpoints will also be explored:
• NIHSS
• BI
• GOS
• Stroke recurrence (based on AE monitoring) within 90 days
• Cognition and behavior (modified 30-minute battery: Controlled Oral Word Association test; Hopkins Verbal Learning Test-Revised [HVLT-R] trials 1, 2, and 3; digit symbol coding from the Wechsler Adult Intelligence Scale III [WAIS III]; Forward and Backward Digit Span test; Benton Judgment of Line Orientation, form V; HVLT-R trial 4 and recognition; semantic fluency [Animal Naming test]; and Boston Naming Test [BNT; 15-item short form]) at Day 90
• Ambulatory performance (as measured by walking speed) at Day 90
• Center for Epidemiologic Studies-Depression (CES-D)
• Quality of life (European Quality of Life [EQ-5D] questionnaire) at Day 90
• Stroke Impact Scale-16 (SIS-16) at Day 90

Inclusion Criteria

Inclusion Criteria
Patients must meet the following criteria for study entry:
• Age ≥ 18 years (no upper age limit)
• Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of ≤5 and determined to be not clearly disabling by the investigator. This includes patients with persistently mild deficits as well as those who improve to a pre-treatment NIHSS score ≤ 5 (also known as RISS).
• Study treatment can be initiated within 3 hours of last known well time without stroke symptoms (i.e., last seen normal).
• Signed informed consent prior to initiation of any study-specific procedure or treatment. The patient or the patient’s legally authorized representative must be able to provide written informed consent and understand the potential risks and benefits from study enrollment and treatment.

 

Exclusion Criteria

Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
• CT or MRI findings consisting of one of the following:
– CT with clear large hypodensity that is greater than one-third middle cerebral artery (MCA) territory (or greater than 100 cc if not in MCA territory),
– MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory),
– Imaging lesion consistent with acute hemorrhage of any degree, OR
– Evidence of intraparenchymal tumor
• Disability prior to the presenting stroke (historical mRS score ≥ 2)
• Standard contraindications to IV alteplase for patients treated within 3 hours of symptom onset, including:
– Head trauma or previous stroke within the previous 3 months
– Myocardial infarction within the previous 3 months
– Gastrointestinal or urinary tract hemorrhage within the previous 21 days
– Major surgery within the previous 14 days
– Arterial puncture at a non-compressible site within the previous 7 days
– Any history of ICH with the exception of < 5 chronic microbleeds on MRI
– Elevated blood pressure (systolic > 185 mm Hg or diastolic >110 mm Hg), or the use of aggressive measures (use of more than two intravenous agents to lower blood pressure) to achieve blood pressure within acceptable parameters
– Treatment with unfractionated heparin within the last 48 hours and activated partial thromboplastin time (aPTT) outside of the normal range as specified by the center’s local laboratory
– Blood glucose <50 mg/dL
– International normalized ratio (INR) > 1.7 (Note: This does not need to be verified prior to randomization if there is no clinical suspicion of abnormality.)
– Platelet count of < 100,000/mm3 (Note: This does not need to be verified prior to randomization if there is no clinical suspicion of abnormality.)
– Treatment with a direct thrombin inhibitor or factor Xa inhibitor (including novel oral anticoagulants [e.g., dabigatran, rivaroxaban, apixaban, edoxaban]) within the last 48 hours
– Treatment with a low-molecular-weight heparin (e.g., dalteparin, enoxaparin) within the last 48 hours
• Allergic reactions to study drug,aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs)
• Females of childbearing age who are known to be pregnant and/or lactating, or who have a positive pregnancy test on admission
• Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet
• Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days
• Current or recent (within 3 months) participation in another investigational drug treatment protocol
• Anticipated inability to obtain 3-month follow-up assessments
• Previous enrollment in PRISMS
• Any other condition that the investigator feels would pose a significant hazard to the patient if treatment with alteplase is initiated