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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02072226
Recruitment Status : Terminated (The study was terminated due to slow enrollment.)
First Posted : February 26, 2014
Results First Posted : July 3, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Stroke Drug: Alteplase Drug: Alteplase Placebo Drug: Aspirin Drug: Aspirin Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 313 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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 Minor Neurologic Deficits (PRISMS)
Actual Study Start Date : May 31, 2014
Actual Primary Completion Date : March 22, 2017
Actual Study Completion Date : March 22, 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Alteplase Placebo + Aspirin
Participants will receive single dose of IV alteplase placebo and aspirin orally.
 Drug: Alteplase Placebo
Single dose of alteplase placebo will be administered as IV injection.

Drug: Aspirin
Single dose of aspirin will be administered at 325 mg orally.
Experimental: Alteplase + Aspirin Placebo
Participants will receive single dose of IV alteplase and aspirin placebo orally.
 Drug: Alteplase
Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).
Other Name: Activase; RO5532960

Drug: Aspirin Placebo
Single dose of aspirin placebo will be administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90 [ Time Frame: Day 90 ]
    mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death prior to Day 90. Reported is the percentage of participants with scores of 0 or 1 on the mRS.


Secondary Outcome Measures :
  1. Distribution of Participants Across the Ordinal mRS [ Time Frame: Day 90 ]
    mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death before Day 90. Reported are the percentages of participants for all scores on the mRS.

  2. Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS [ Time Frame: Day 90 ]
    Global favorable recovery is an integrated assessment of participants who meet the following: mRS Score 0-1, National Institutes of Health Stroke Scale (NIHSS) Score 0-1, Barthel Index [BI] greater than or equal to 95, and Glasgow Outcome Scale [GOS] equal to 1. mRS Score 0-1: 0= No symptoms at all, 1= No significant disability despite symptoms, able to carry out all usual duties and activities. NIHSS Score 0-1: 0= No stroke symptoms and 1= Minor stroke symptoms. BI is a 10 question index with a total score range of 0-100 with 100 being the best outcome. GOS =1: Good recovery. Reported here are the percentages of participants who achieved a favorable score on each of these scales.

  3. Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH ) [ Time Frame: Within 36 hours after study drug administration on Day 1 ]
    ICH was considered symptomatic if it was not seen on computed tomography (CT) or magnetic resonance imaging (MRI) scan at baseline and any neurologic decline was attributed to it by the local investigator. To detect intracranial hemorrhage, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.

  4. Percentage of Participants With Any ICH [ Time Frame: Within 36 hours after study drug administration on Day 1 ]
    To detect ICH, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.

  5. Overall Mortality [ Time Frame: From baseline to Day 90 ]
    Reported here is the percentage of participants who died due to any cause during the study.

  6. Percentage of Participants Who Died Due to Stroke and Neurological Disorders [ Time Frame: From baseline to Day 90 ]
    Reported here is the percentage of participants who died due to stroke and neurological disorders.

  7. Percentage of Participants With Adverse Events [ Time Frame: From baseline up to Day 90: Non-serious adverse events were collected through the Day 30 visit. Serious adverse events were collected through the end of study at Day 90. ]
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  8. Percentage of Participants With Serious Adverse Events [ Time Frame: From baseline to Day 90 ]
    A serious adverse event (SAE) was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02072226


Locations
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Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Genentech, Inc.
  Study Documents (Full-Text)

Documents provided by Genentech, Inc.:
Statistical Analysis Plan  [PDF] May 17, 2017
Study Protocol  [PDF] January 8, 2015

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02072226    
Other Study ID Numbers: ML29093
First Posted: February 26, 2014    Key Record Dates
Results First Posted: July 3, 2018
Last Update Posted: July 3, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Aspirin
Tissue Plasminogen Activator
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
 Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics