A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Genentech, Inc.
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
First received: February 24, 2014
Last updated: November 2, 2015
Last verified: November 2015

PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) Activase in patients with mild acute ischemic strokes that do not appear to be clearly disabling.

Patients will be randomized in a 1:1 ratio to receive within 3 hours of last known well time either 1) one dose of IV Activase and one dose of oral aspirin placebo or 2) one dose of IV Activase placebo and one dose of oral aspirin 325 mg.

Condition Intervention Phase
Brain Ischemia
Drug: alteplase [Activase]
Drug: alteplase placebo
Drug: aspirin
Drug: aspirin placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIIB, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Neurologic Deficits (PRISMS)

Resource links provided by NLM:

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 [ Time Frame: Assessed at Day 90 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in NIH Stroke Scale (NIHSS) score [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Measure of daily functioning (Barthel Index score) at end of study [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  • Assessment of disability due to brain injury using Glasgow Outcome Scale [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  • Incidence of symptomatic intracranial hemmorhage or any intracranial hemorrhage [ Time Frame: 36 hours ] [ Designated as safety issue: No ]
  • Overall mortality [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 948
Study Start Date: May 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aspirin Drug: alteplase placebo
single intravenous dose
Drug: aspirin
325 mg oral dose
Experimental: alteplase [Activase] Drug: alteplase [Activase]
single intravenous dose of 0.9 mg/kg with a maximal dose of 90mg
Drug: aspirin placebo
Single oral dose


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age >/= 18 years.
  • Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of </= 5 and determined as not clearly disabling by the investigator.
  • Study treatment initiated within 3 hours of last time patient seen normal.

Exclusion Criteria:

  • Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:

    • Clear large hypodensity on CT (or hyperintensity on MRI) > one-third middle cerebral artery (MCA) territory or > 100 cc if not in MCA territory, OR
    • Imaging lesion consistent with acute hemorrhage, OR
    • Evidence of intraparenchymal tumor
  • Disability prior to the presenting stroke
  • Standard contraindications to IV alteplase within 3 hrs of symptom onset including:

    • Head trauma, myocardial infarction, or stroke within past 3 months
    • Gastrointestinal or urinary tract hemorrhage within past 21 days
    • Major surgery within past 14 days
    • Arterial puncture at non-compressible site within past 7 days
    • Any history of intracranial hemorrhage (excepting those < 5 chronic microbleeds on MRI
    • Elevated blood pressure defined by systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg, OR treatments requiring aggressive measures to achieve acceptable levels
    • Treatment with heparin within past 48 hrs AND an activated partical thromboplasting time outside normal
    • Blood glucose < 50 mg/dL
    • International normalized ratio > 1.7
    • Platelet count < 100,000/cm3
    • Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban,edoxaban) within the last 48 hrs
  • Allergic reaction to study drug or aspirin
  • Females of childbearing age who are known to be pregnant and/or lactating
  • Inability to swallow aspirin or aspirin placebo capsule
  • Other serious 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 patient with alteplase treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02072226

Contact: Reference Study ID Number: ML29093 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Show 86 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Study Director: Clinical Trials Genentech, Inc.
  More Information

Additional Information:
No publications provided by Genentech, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02072226     History of Changes
Other Study ID Numbers: ML29093
Study First Received: February 24, 2014
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Ischemia
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Tissue Plasminogen Activator
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2015