Clinical trial NCT02072226: A Study of the Efficacy and Safety of Alteplase in Participants With Mild Stroke
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Stroke
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2014-02-26
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90
timeFrame: Day 90
Secondary outcomes:
measure: Distribution of Participants Across the Ordinal mRS
timeFrame: Day 90
measure: Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS
timeFrame: Day 90
measure: Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )
timeFrame: Within 36 hours after study drug administration on Day 1
measure: Percentage of Participants With Any ICH
timeFrame: Within 36 hours after study drug administration on Day 1
measure: Overall Mortality
timeFrame: From baseline to Day 90
measure: Percentage of Participants Who Died Due to Stroke and Neurological Disorders
timeFrame: From baseline to Day 90
measure: Percentage of Participants With Adverse Events
timeFrame: 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.
measure: Percentage of Participants With Serious Adverse Events
timeFrame: From baseline to Day 90
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Loveland
country: United States
facility: Medical Center of The Rockies
state: Colorado
city: Danbury
country: United States
facility: Associated Neurologists PC
state: Connecticut
city: Fairfield
country: United States
facility: Associated Neurologists of Southern CT PC
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Services; Sponsor Programs Ammon Education Center
state: Delaware
city: Bradenton
country: United States
facility: Nova Clinical Research, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Neurologic Consultants, P.A.
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine; Clinical Reseach Building
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neuroscience Institute
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Edgewood
country: United States
facility: St. Elizabeth Edgewood; Cancer Care Center" for Account St. Elizabeth Edgewood
state: Kentucky
city: Elizabethtown
country: United States
facility: University of Louisville
state: Kentucky
city: Florence
country: United States
facility: St. Elizabeth Florence
state: Kentucky
city: Fort Thomas
country: United States
facility: St. Elizabeth Fort Thomas
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Randallstown
country: United States
facility: Northwest Hospital Center
state: Maryland
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Health System
state: Michigan
city: Pontiac
country: United States
facility: St Joesph Mercy Hospital Oakland
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
city: Golden Valley
country: United States
facility: The Minneapolis Clinic of Neurology
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Reno
country: United States
facility: Renown Health; Renown Institute for Neurosciences
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Toms River
country: United States
facility: Shore Neurology
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center.
state: New York
city: Brooklyn
country: United States
facility: Lutheran Medical Center
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center
state: New York
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill
state: North Carolina
city: Greensboro
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: West Hospital
state: Ohio
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Jewish Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Anderson Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Dayton
country: United States
facility: Wright State University
state: Ohio
city: Fairfield
country: United States
facility: Fairfield Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent's Medical Center
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Healthcare Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina; MSC 300
state: South Carolina
city: Columbia
country: United States
facility: University of South Carolina School of Medicine
state: South Carolina
city: Orangeburg
country: United States
facility: The Neurology And Pain Clinic
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Houston
country: United States
facility: Methodist Neurological Institute
state: Texas
city: Houston
country: United States
facility: University Of Texas Health Science Center Houston
state: Texas
city: Lubbock
country: United States
facility: Texas Tech Univ Health Sci Ctr
state: Texas
city: San Antonio
country: United States
facility: University Hospital San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah
state: Utah
city: Fairfax
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: La Crosse
country: United States
facility: Gunderson Health System
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.