NCT02072226

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).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
313

participants targeted

Target at P50-P75 for phase_3 stroke

Timeline
Completed

Started May 2014

Geographic Reach
1 country

88 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 24, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 26, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

May 31, 2014

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 22, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 22, 2017

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

July 3, 2018

Completed
Last Updated

July 3, 2018

Status Verified

June 1, 2018

Enrollment Period

2.8 years

First QC Date

February 24, 2014

Results QC Date

March 7, 2018

Last Update Submit

June 4, 2018

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at 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.

    Day 90

Secondary Outcomes (8)

  • Distribution of Participants Across the Ordinal mRS

    Day 90

  • Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS

    Day 90

  • Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )

    Within 36 hours after study drug administration on Day 1

  • Percentage of Participants With Any ICH

    Within 36 hours after study drug administration on Day 1

  • Overall Mortality

    From baseline to Day 90

  • +3 more secondary outcomes

Study Arms (2)

Alteplase Placebo + Aspirin

ACTIVE COMPARATOR

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

Drug: Alteplase PlaceboDrug: Aspirin

Alteplase + Aspirin Placebo

EXPERIMENTAL

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

Drug: AlteplaseDrug: Aspirin Placebo

Interventions

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

Also known as: Activase; RO5532960
Alteplase + Aspirin Placebo

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

Alteplase Placebo + Aspirin

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

Alteplase Placebo + Aspirin

Single dose of aspirin placebo will be administered orally.

Alteplase + Aspirin Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:
  • 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)
  • 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, or
  • Evidence of intraparenchymal tumor
  • Disability prior to the presenting stroke
  • Standard contraindications to IV alteplase within 3 hours of symptom onset, including:
  • Head trauma, myocardial infarction, or previous stroke 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 non-compressible site within the previous 7 days
  • Any history of ICH with the exception of those less than (\<) 5 chronic microbleeds on MRI
  • 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
  • Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range
  • Blood glucose \<50 milligrams per deciliter (mg/dL)
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (88)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

Location

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

University of Arizona

Tucson, Arizona, 85724-5030, United States

Location

St. Jude Medical Center

Fullerton, California, 92835, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Hoag Memorial Hospital

Newport Beach, California, 92658, United States

Location

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

Colorado Neurological Institute

Englewood, Colorado, 80113, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Medical Center of The Rockies

Loveland, Colorado, 80538, United States

Location

Associated Neurologists PC

Danbury, Connecticut, 06810, United States

Location

Associated Neurologists of Southern CT PC

Fairfield, Connecticut, 06824, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Christiana Care Health Services; Sponsor Programs Ammon Education Center

Newark, Delaware, 19718-0002, United States

Location

Nova Clinical Research, LLC

Bradenton, Florida, 34209, United States

Location

Neurologic Consultants, P.A.

Fort Lauderdale, Florida, 33308, United States

Location

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612-3244, United States

Location

Alexian Brothers Neuroscience Institute

Elk Grove Village, Illinois, 60007, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

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

Edgewood, Kentucky, 41017, United States

Location

University of Louisville

Elizabethtown, Kentucky, 42791, United States

Location

St. Elizabeth Florence

Florence, Kentucky, 41042, United States

Location

St. Elizabeth Fort Thomas

Fort Thomas, Kentucky, 41075, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Northwest Hospital Center

Randallstown, Maryland, 21133, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Sparrow Health System

Lansing, Michigan, 48909, United States

Location

St Joesph Mercy Hospital Oakland

Pontiac, Michigan, 48341, United States

Location

Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

The Minneapolis Clinic of Neurology

Golden Valley, Minnesota, 55422, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65212, United States

Location

Washington University

St Louis, Missouri, 63128, United States

Location

Renown Health; Renown Institute for Neurosciences

Reno, Nevada, 89502, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Overlook Hospital

Summit, New Jersey, 07902, United States

Location

Shore Neurology

Toms River, New Jersey, 08755, United States

Location

SUNY Downstate Medical Center.

Brooklyn, New York, 11203, United States

Location

Lutheran Medical Center

Brooklyn, New York, 11220, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Guilford Neurologic Associates

Greensboro, North Carolina, 27401, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45203-0542, United States

Location

West Hospital

Cincinnati, Ohio, 45211, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Jewish Hospital

Cincinnati, Ohio, 45236, United States

Location

Anderson Hospital

Cincinnati, Ohio, 45255, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Wright State University

Dayton, Ohio, 45409, United States

Location

Fairfield Hospital

Fairfield, Ohio, 45014, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Providence Saint Vincent's Medical Center

Portland, Oregon, 97225, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18105, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, 19141, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15219, United States

Location

York Hospital

York, Pennsylvania, 17403, United States

Location

Medical University of South Carolina; MSC 300

Charleston, South Carolina, 29425, United States

Location

University of South Carolina School of Medicine

Columbia, South Carolina, 29203-7606, United States

Location

The Neurology And Pain Clinic

Orangeburg, South Carolina, 29118, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37404, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78550, United States

Location

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University Of Texas Health Science Center Houston

Houston, Texas, 77030, United States

Location

Texas Tech Univ Health Sci Ctr

Lubbock, Texas, 79430, United States

Location

University Hospital San Antonio

San Antonio, Texas, 78229, United States

Location

University Of Utah

Salt Lake City, Utah, 84108, United States

Location

Inova Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

Gunderson Health System

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen ActivatorAspirin

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological FactorsSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Limitations and Caveats

The study was terminated early due to low enrollment, leading to smaller number of participants analyzed.

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche

Study Officials

  • Clinical Trials

    Genentech, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 24, 2014

First Posted

February 26, 2014

Study Start

May 31, 2014

Primary Completion

March 22, 2017

Study Completion

March 22, 2017

Last Updated

July 3, 2018

Results First Posted

July 3, 2018

Record last verified: 2018-06

Locations