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

NCT ID: NCT02072226

Last Updated: 2018-07-03

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

313 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2017-03-22

Brief Summary

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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).

Detailed Description

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Conditions

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Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Alteplase Placebo + Aspirin

Participants will receive single dose of IV alteplase placebo and aspirin orally.

Group Type ACTIVE_COMPARATOR

Alteplase Placebo

Intervention Type DRUG

Single dose of alteplase placebo will be administered as IV injection.

Aspirin

Intervention Type DRUG

Single dose of aspirin will be administered at 325 mg orally.

Alteplase + Aspirin Placebo

Participants will receive single dose of IV alteplase and aspirin placebo orally.

Group Type EXPERIMENTAL

Alteplase

Intervention Type DRUG

Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).

Aspirin Placebo

Intervention Type DRUG

Single dose of aspirin placebo will be administered orally.

Interventions

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Alteplase

Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).

Intervention Type DRUG

Alteplase Placebo

Single dose of alteplase placebo will be administered as IV injection.

Intervention Type DRUG

Aspirin

Single dose of aspirin will be administered at 325 mg orally.

Intervention Type DRUG

Aspirin Placebo

Single dose of aspirin placebo will be administered orally.

Intervention Type DRUG

Other Intervention Names

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Activase; RO5532960

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

St. Jude Medical Center

Fullerton, California, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital

Newport Beach, California, United States

Site Status

University of California Los Angeles

Santa Monica, California, United States

Site Status

Colorado Neurological Institute

Englewood, Colorado, United States

Site Status

Poudre Valley Hospital

Fort Collins, Colorado, United States

Site Status

Medical Center of The Rockies

Loveland, Colorado, United States

Site Status

Associated Neurologists PC

Danbury, Connecticut, United States

Site Status

Associated Neurologists of Southern CT PC

Fairfield, Connecticut, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Christiana Care Health Services; Sponsor Programs Ammon Education Center

Newark, Delaware, United States

Site Status

Nova Clinical Research, LLC

Bradenton, Florida, United States

Site Status

Neurologic Consultants, P.A.

Fort Lauderdale, Florida, United States

Site Status

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Alexian Brothers Neuroscience Institute

Elk Grove Village, Illinois, United States

Site Status

Parkview Research Center

Fort Wayne, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

St. Elizabeth Edgewood; Cancer Care Center" for Account St. Elizabeth Edgewood

Edgewood, Kentucky, United States

Site Status

University of Louisville

Elizabethtown, Kentucky, United States

Site Status

St. Elizabeth Florence

Florence, Kentucky, United States

Site Status

St. Elizabeth Fort Thomas

Fort Thomas, Kentucky, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Northwest Hospital Center

Randallstown, Maryland, United States

Site Status

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status

Sparrow Health System

Lansing, Michigan, United States

Site Status

St Joesph Mercy Hospital Oakland

Pontiac, Michigan, United States

Site Status

Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

The Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri Health Care

Columbia, Missouri, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Renown Health; Renown Institute for Neurosciences

Reno, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

Site Status

Shore Neurology

Toms River, New Jersey, United States

Site Status

SUNY Downstate Medical Center.

Brooklyn, New York, United States

Site Status

Lutheran Medical Center

Brooklyn, New York, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

Ichan School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Guilford Neurologic Associates

Greensboro, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Akron General Medical Center

Akron, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

West Hospital

Cincinnati, Ohio, United States

Site Status

The Christ Hospital

Cincinnati, Ohio, United States

Site Status

Jewish Hospital

Cincinnati, Ohio, United States

Site Status

Anderson Hospital

Cincinnati, Ohio, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Wright State University

Dayton, Ohio, United States

Site Status

Fairfield Hospital

Fairfield, Ohio, United States

Site Status

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Saint Vincent's Medical Center

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

York Hospital

York, Pennsylvania, United States

Site Status

Medical University of South Carolina; MSC 300

Charleston, South Carolina, United States

Site Status

University of South Carolina School of Medicine

Columbia, South Carolina, United States

Site Status

The Neurology And Pain Clinic

Orangeburg, South Carolina, United States

Site Status

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, United States

Site Status

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status

Valley Baptist Medical Center

Harlingen, Texas, United States

Site Status

Methodist Neurological Institute

Houston, Texas, United States

Site Status

University Of Texas Health Science Center Houston

Houston, Texas, United States

Site Status

Texas Tech Univ Health Sci Ctr

Lubbock, Texas, United States

Site Status

University Hospital San Antonio

San Antonio, Texas, United States

Site Status

University Of Utah

Salt Lake City, Utah, United States

Site Status

Inova Fairfax Hospital

Fairfax, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

West Virginia University Hospital

Morgantown, West Virginia, United States

Site Status

Gunderson Health System

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Khatri P, Kleindorfer DO, Devlin T, Sawyer RN Jr, Starr M, Mejilla J, Broderick J, Chatterjee A, Jauch EC, Levine SR, Romano JG, Saver JL, Vagal A, Purdon B, Devenport J, Pavlov A, Yeatts SD; PRISMS Investigators. Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits: The PRISMS Randomized Clinical Trial. JAMA. 2018 Jul 10;320(2):156-166. doi: 10.1001/jama.2018.8496.

Reference Type DERIVED
PMID: 29998337 (View on PubMed)

Zhao W, Mu Y, Tayama D, Yeatts SD. Comparison of statistical and operational properties of subject randomization procedures for large multicenter clinical trial treating medical emergencies. Contemp Clin Trials. 2015 Mar;41:211-8. doi: 10.1016/j.cct.2015.01.013. Epub 2015 Jan 29.

Reference Type DERIVED
PMID: 25638754 (View on PubMed)

Choi JC, Jang MU, Kang K, Park JM, Ko Y, Lee SJ, Cha JK, Kim DH, Park SS, Park TH, Lee KB, Lee J, Kim JT, Cho KH, Yu KH, Oh MS, Lee BC, Cho YJ, Kim DE, Lee JS, Lee J, Gorelick PB, Bae HJ. Comparative effectiveness of standard care with IV thrombolysis versus without IV thrombolysis for mild ischemic stroke. J Am Heart Assoc. 2015 Jan 27;4(1):e001306. doi: 10.1161/JAHA.114.000596.

Reference Type DERIVED
PMID: 25628404 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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ML29093

Identifier Type: -

Identifier Source: org_study_id

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