A Study of the Efficacy and Safety of Alteplase in Participants With Mild Stroke
Condition: Stroke
MeSH terms: Stroke
Intervention: Alteplase; Alteplase Placebo; Aspirin; Aspirin Placebo
Intervention description: Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).; Single dose of alteplase placebo will be administered as IV injection.; Single dose of aspirin will be administered at 325 mg orally.; Single dose of aspirin placebo will be administered orally.
Intervention MeSH terms: Aspirin; Tissue Plasminogen Activator
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 313.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy
      and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes
      that do not appear to be clearly disabling. Participants will be randomized in a 1:1 ratio to
      receive within 3 hours of last known well time either 1) one dose of IV alteplase and one
      dose of oral aspirin placebo or 2) one dose of IV alteplase placebo and one dose of oral
      aspirin 325 milligrams (mg).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than
             or equal to(</=) 5 and determined as not clearly disabling by the investigator

          -  Study treatment initiated within 3 hours of last time participant seen normal

        Exclusion Criteria:

          -  Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the
             following:

               1. CT with clear large hypodensity that is greater than (>) one-third middle
                  cerebral artery (MCA) territory (or >100 cubic centimeter [cc] if not in MCA
                  territory)

               2. 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),

               3. Imaging lesion consistent with acute hemorrhage, or

               4. Evidence of intraparenchymal tumor

          -  Disability prior to the presenting stroke

          -  Standard contraindications to IV alteplase within 3 hours of symptom onset, including:

               1. Head trauma, myocardial infarction, or previous stroke within the previous 3
                  months

               2. Gastrointestinal or urinary tract hemorrhage within the previous 21 days

               3. Major surgery within the previous 14 days

               4. Arterial puncture at non-compressible site within the previous 7 days

               5. Any history of ICH with the exception of those less than (<) 5 chronic
                  microbleeds on MRI

               6. Elevated blood pressure defined by systolic blood pressure >185 millimeters of
                  mercury (mm Hg) or diastolic blood pressure >110 mm Hg, or treatments requiring
                  aggressive measures to achieve acceptable levels

               7. Treatment with unfractioned heparin within past 48 hours and activated partial
                  thromboplastin time outside normal range

               8. Blood glucose <50 milligrams per deciliter (mg/dL)

               9. International normalized ratio >1.7

              10. Platelet count <100,000 per cubic millimeter (/mm^3)

              11. Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor
                  (apixaban, rivaroxaban, edoxaban) within the last 48 hours

          -  Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs
             (NSAIDs)

          -  Females of childbearing age who are known to be pregnant and/or lactating

          -  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 deemed by the investigator that would pose hazard to the
             participant with alteplase treatment